Autism Genome Project delivers genetic discovery

A new study from investigators with the Autism Genome Project (AGP), the world's largest research project on identifying genes associated with risk for autism, has found that the comprehensive use of copy number variant (CNV) genetic testing offers an important tool in individualized diagnosis and treatment of autism.

Funded primarily by Autism Speaks, the world's leading autism science and advocacy organization, the Autism Genome Project (AGP) involved more than 50 research centers in 11 countries.

The report, published today in the American Journal of Human Genetics, delivers on the 10-year project's objective to provide practical methods for earlier diagnosis and personalized treatment of autism.

Rob Ring

"With the publication of this study, we should step back to recognize and celebrate the pioneering achievements of the AGP and what they have accomplished in helping to launch the field of genomic risk discovery in autism," says Autism Speaks Chief Science Officer Rob Ring.

"The AGP has generated information that holds the potential to guide medical care for certain individuals with autism today."

"They have demonstrated that science can work for families, and Autism Speaks is proud to have been a supporter of the work all along the way."

The study involved CNV testing of 2,446 families affected by autism and 4,768 individuals unaffected by neurologic or psychiatric disorders.

Overall, CNV s were significantly more common in the participating families affected by autism and, the CNV testing uncovered dozens of cases where autism-linked gene changes were associated with additional health risks warranting medical attention.

In nine of the families affected by autism, CNV s involved a gene that indicates elevated risk for seizures and epilepsy.

Stephen Scherer

"This result warrants an immediate referral to a neurologist," explains senior author Stephen Scherer of the Toronto's Hospital for Sick Children and the University of Toronto.

Similarly, CNV  testing indicated a high risk for Duchene muscular dystrophy in several of the autism families and identified syndromes associated with heart problems in others.

CNV s are genetic changes that involve duplication or deletion of entire segments of DNA.

They do not typically show up on standard genetic tests which search for "spelling mistakes" in the DNA letters that compose a gene.

Those standard tests identify a clear genetic autism link in only 15 to 20 percent of the cases.

"This report and its extensive supplements should become a new guidebook for medical geneticists working with families affected by autism," Dr. Scherer says.

In addition, the study added dozens of genes to the growing list of those that contribute to the development of autism.

Surprisingly, the autism genes identified through CNV testing had little overlap with those detected using standard exome gene sequencing, yet researchers say they affect the same brain pathways.

"These gene discoveries will help guide further research on autism subtypes and their treatment," Dr. Scherer says.

In response, the investigators urge medical geneticists to add CNV testing to the standard gene tests for autism and to consult medical recommendations for the many autism-linked syndromes that CNV testing can reveal.

CNV testing is currently available, though it's not typically part of standard genetic testing for autism.

Whole genome sequencing is the next step in genetic testing for Autism but is not yet widely available in ordinary medical settings.

Autism Speaks has taken a world-leadership position in in this direction with its Autism Ten Thousand Genomes (Aut10K) program.

More Information: "Convergence of Genes and Cellular Pathways Dysregulated in Autism Spectrum Disorders" American Journal of Human Genetics: ((2014), doi.org/10.1016/j.ajhg.2014.03.018

Genetic discovery could increase understanding of ADHD

Scientists at Trinity College Dublin have discovered that a mutation in a single gene involved in the functioning of the brain's nervous system can lead to hyperactivity symptoms that are characteristic of Attention-Deficit Hyperactivity Disorder (ADHD).

Getting the nervous system wired up properly is a big job. The brain contains billions of different types of nerve cells, which all have to be connected in a very precise fashion.

This circuitry self-assembles as an embryo grows, based on a developmental programme involving the actions of thousands of different genes.

The scientists discovered that a mutation in a single mouse gene, 'Elfn1', can have a big effect.

Their new findings give impetus to discover whether mutations in Elfn1 in humans can give rise to similar symptoms and whether they might play a part in some patients with epilepsy and ADHD.

These two conditions occur together far more often than expected by chance.

In an article just published in the international journal, PLOS ONE, Associate Professor in Genetics at Trinity, Kevin Mitchell, and Research Technical Officer, Dr Jackie Dolan, investigated the importance of the function played by Elfn1 and the protein it produces when expressed.

They did this by experimentally removing it from some mice and comparing the effects against those seen in mice with the normal gene.

Although overall brain anatomy and patterns of connectivity remained normal, there was clear evidence of disturbance in brain function in individuals without Elfn1.

Seizures occurred in some, and these became more common over time and were easily triggered by human interaction.

Secondly, hyperactivity was observed, and this showed an unusual response to the stimulant, amphetamine.

Amphetamine normally causes hyperactivity in animals that have Elfn1 present, as it does in most humans. Here, it reduced the hyperactivity of the mice without the gene.

This is similar to the situation in patients with ADHD, where amphetamine and related drugs have a paradoxical, calming effect.

"These findings clearly show that removal of the Elfn1 gene affects brain circuits with multiple consequences for behaviour," said Dr Dolan.

The seizures likely relate to the function of Elfn1 in dampening the response of the nervous system to strong stimuli in key brain structures called the cortex and hippocampus.

However, the development of ADHD-like hyperactivity focused on a different brain structure, known as the habenula.

This structure is part of a system that integrates information from multiple regions of the brain and regulates the activity of nerve cells that produce mood-regulating chemicals such as dopamine and serotonin.

Professor Mitchell said: "We are at the beginning of this process of figuring out how this gene works and understanding the consequences when it is mutated but, these animals provide a unique model to investigate how subtle changes in brain development can ultimately result in aberrant brain function".

Elfn1 was first discovered by Dr Dolan, Professor Mitchell and colleagues in 2007. The protein it produces when expressed allows communication from one nerve cell to another. In a study published in Science last year, Emily Sylwestrak and Anirvan Ghosh, of the University of California, San Diego, showed that the Elfn1 protein determined what kind of connection was made onto those nerve cells.

More information: dx.plos.org/10.1371/journal.pone.008049

Autism ASD: Researchers discover a potential cause

Topoisomerase inhibitors reduce the expression of long genes in neurons, including a remarkable number of genes implicated in Autism Spectrum Disorders -- 200 kb is four times longer than the average gene. 

Credit: Concept: Mark Zylka. Illustration: Janet Iwasa.

Problems with a key group of enzymes called topoisomerases can have profound effects on the genetic machinery behind brain development and potentially lead to autism spectrum disorder (ASD), according to research announced today in the journal Nature.

Scientists at the University of North Carolina School of Medicine have described a finding that represents a significant advance in the hunt for environmental factors behind autism and lends new insights into the disorder's genetic causes.

"Our study shows the magnitude of what can happen if topoisomerases are impaired," said senior study author Mark Zylka, PhD, associate professor in the Neuroscience Center and the Department of Cell Biology and Physiology at UNC.

"Inhibiting these enzymes has the potential to profoundly affect neurodevelopment—perhaps even more so than having a mutation in any one of the genes that have been linked to autism."

The study could have important implications for ASD detection and prevention.

Mark Zylka

"This could point to an environmental component to autism," said Zylka.

"A temporary exposure to a topoisomerase inhibitor in utero has the potential to have a long-lasting effect on the brain, by affecting critical periods of brain development. "

This study could also explain why some people with mutations in topoisomerases develop autism and other neuro-developmental disorders.

Topiosomerases are enzymes found in all human cells. Their main function is to untangle DNA when it becomes overwound, a common occurrence that can interfere with key biological processes.

Most of the known topoisomerase-inhibiting chemicals are used as chemotherapy drugs. Zylka said his team is searching for other compounds that have similar effects in nerve cells.

"If there are additional compounds like this in the environment, then it becomes important to identify them," said Zylka.

"That's really motivating us to move quickly to identify other drugs or environmental compounds that have similar effects—so that pregnant women can avoid being exposed to these compounds."

Zylka and his colleagues stumbled upon the discovery quite by accident while studying topotecan, a topoisomerase-inhibiting drug that is used in chemotherapy.

Investigating the drug's effects in mouse and human-derived nerve cells, they noticed that the drug tended to interfere with the proper functioning of genes that were exceptionally long—composed of many DNA base pairs.

The group then made the serendipitous connection that many autism-linked genes are extremely long.

"That's when we had the 'Eureka moment,'" said Zylka. "We realized that a lot of the genes that were suppressed were incredibly long autism genes."

Of the more than 300 genes that are linked to autism, nearly 50 were suppressed by topotecan. Suppressing that many genes across the board—even to a small extent—means a person who is exposed to a topoisomerase inhibitor during brain development could experience neurological effects equivalent to those seen in a person who gets ASD because of a single faulty gene.

The study's findings could also help lead to a unified theory of how autism-linked genes work. About 20 percent of such genes are connected to synapses—the connections between brain cells.

Another 20 percent are related to gene transcription—the process of translating genetic information into biological functions.

Zylka said this study bridges those two groups, because it shows that having problems transcribing long synapse genes could impair a person's ability to construct synapses.

"Our discovery has the potential to unite these two classes of genes—synaptic genes and transcriptional regulators," said Zylka.

"It could ultimately explain the biological mechanisms behind a large number of autism cases."

More information: Nature paper dx.doi.org/10.1038/nature12504

The Power of a Mother's touch

Mothers who stroke their baby's body in the first few weeks after birth may change the effects that stress during pregnancy can have on an infant's early-life development, researchers have found.

Researchers at the Universities of Liverpool, Manchester, and Kings College, London have been studying whether stress in pregnancy can lead to emotional and behavioural problems in children for many years.

Attention is now moving towards how parents might alter these effects after birth.

Researchers are aiming to improve understanding of the issues to help enhance information services for pregnant women and their partners.

Scientists believe that stress in pregnancy can have an effect on an infant in later life by reducing the activity of genes that play a role in stress response.

Studies of early care-giving in rats have found that high levels of mothers' licking and grooming their pups soon after birth can increase the activity of these genes and may reverse the effects of prenatal stress on their offspring.

Some studies suggest that impacts of prenatal stress on an infant's development can be either positive or negative depending on the type of environment a child encounters. It is thought that some children may experience the effects through being more prone to high levels of fear or anger.

The team at Liverpool, Manchester and London followed first-time mothers from pregnancy through to the first years of their children's lives as part of Medical Research Council (MRC) funded research, The Wirral Child Health and Development Study.

It showed that links between symptoms of depression in pregnancy and subsequent infant emotions of fear and anger, as well as heart rate response to stress at seven months of age changed by how often a mother stroked their baby on the head, back, legs and arms in the early weeks of life.

The results suggest that stroking may alter gene activity in a similar way to that reported in animals.

Dr Helen Sharp, from the University of Liverpool's Institute of Psychology, Health and Society, explains: "We are currently following up on the Wirral children in our study to see if reports of early stroking by their mothers continue to make a difference to developmental outcomes over time.

"The eventual aim is to find out whether we should recommend that mothers who have been stressed during pregnancy should be encouraged to stroke their babies early in life"

The study is published in the journal PLOS ONE.

Smart Babies: Research Explores Infants' Skills and Abilities

Infants seem to develop at an astoundingly rapid pace, learning new things and acquiring new skills every day. And research suggests that the abilities that infants demonstrate early on can shape the development of skills later in life, in childhood and beyond.

How Do You Learn to Walk? Thousands of Steps and Dozens of Falls per Day
In this study, Adolph and colleagues recorded 15- to 60-minute videos of spontaneous activity from infants.

They then coded the videos for the time infants spent walking and crawling, the number of crawling and walking steps infants took, and the number of falls infants experienced whether walking or crawling.

The researchers found that the infants moved a tremendous amount and that new walkers moved faster than crawlers but had a similar number of falls at first and fewer as they became more experienced.

This suggests that infants are motivated to begin walking because they move faster without falling more and that they dramatically improve their walking skills through immense amounts of practice.

Implications of Infant Cognition for Executive Functions at Age 11
Do basic information processing skills in infancy have any bearing on later executive functioning skills in children?

Infants were assessed for memory, processing speed, and attention at age 7-12 months and age 24-36 months.

When they were 11 years old, the children returned to the lab and were assessed for various different kinds of executive functioning skills, including working memory, inhibition, and shifting.

Rose and colleagues created a statistical model that used infant abilities to predict executive functioning later in childhood and they found that this model fit the data well.

The model indicated that processing speed in infancy significantly predicted working memory and shifting ability at age 11 and that memory in infancy significantly predicted shifting at age 11.

This research supports the idea that infant cognitive abilities provide a foundation for the later development of executive functioning abilities.

One-Year-Old Infants Follow Others' Voice Direction
Can infants determine what adults are paying attention to by listening to their voices? Yes!

Rossano and colleagues conducted an experiment in which infants were placed in front of a wooden barrier that had a box sticking out of either side.

A member of the research team hid behind the barrier and spoke in the direction of one of the boxes.

The researchers then watched to see which box the infants moved toward. Rossano and colleagues found that infants moved toward the box that was in the direction of the researcher's vocalisation.

A follow-up study that examined the same task with chimpanzees found that they showed no ability to follow voice direction.

This suggests that infants -- but perhaps not chimpanzees -- can infer what an adult is paying attention to based on voice alone.

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Story Source:

The above story is reprinted from materials provided by Association for Psychological Science.

Dyslexia: Learning Difficulties examined

Learning difficulty, although sometimes called a learning disorder or learning disability, is a classification that includes several disorders, in which a person has difficulty learning in an expected or typical manner.

Learning difficulties;

• are rarely simple, there is normally additional complexity associated with the condition,
• can be isolating and reduces confidence and self esteem,
• can make life problematic for a person to learn as quickly or, more relevantly, in the same way, as others.
• are not indicative of cognition or intelligence level, only indicative of the need for alternative ways in which to learn.
• cannot be 'fixed' or 'cured', only managed,
• make people face unique challenges that last their entire lifetime.

Interventions may be used to help the individual learn or develop strategies that will foster their future success.

The causes of learning difficulties are not always well understood and not always apparent but selectively, some are;

• Common Causes of Learning Difficulties
• How Psychotherapy Can Help with Learning Difficulties
• Learning Difficulties in the DSM

Common Causes of Learning Difficulties
Learning difficulties range from mild, through varying degrees of complexity, to severe but, given support and understanding, people with learning difficulties can and do, lead very normal lives.

Many people with learning difficulties go on to hold very intellectually demanding positions and function at a very high level in our progressive societies.

Some causes of neurological impairments include:

• Accident in baby or childhood - may be caused by malnutrition, head injury or toxic exposure

• Heredity or Genetics - Certain conditions may run in the family

• Poverty - may be a result of a lack of parental reinforcement or affordability of support from specific medical or academic sources

• Problems during pregnancy and/or birth - may result from fetal exposure to alcohol or drugs, oxygen deprivation, anomalies developed in the brain, low birth weight, injury or illness or premature or prolonged labour

One major factor for many people who face learning difficulties is that they are unable to express their feelings easily in words and their actions may have to speak for them.

Their behaviour and moods may change and their inability to express themselves may result in depression, sadness, anxiety and other mental health issues, which are generally treated separately from the underlying condition.

A more 'holistic' view is always more beneficial to the management of your health and welfare and is particularly important in managing learning difficulties.

Can Psychotherapy Help with Learning Difficulties
A diagnosis of any learning difficulty may be potentially devastating to a person and their family.

Both the person who faces learning difficulties and their family members will need to learn coping skills for the difficulty as well as emotionally.

Stress associated with learning difficulties can accumulate which may make the coping process even more difficult and the selection of coping strategies inappropriate.

Learning difficulties are most often present over an entire lifetime, so learning effective and appropriate methods of coping are essential to successful management.

Psychotherapy and the teaching of behavioural strategies or techniques, often work best for individuals who struggle with learning difficulties.

For children, play therapy may be helpful if the therapist uses it to teach interaction techniques. Children and adults may also do well in therapy and most will benefit from joining a mutual support group.

Dyslexia Study: CYP19A1 gene and the linkage region of speech and language disorders

Paper Abstract

Inspired by the localization, on 15q21.2 of the CYP19A1 gene in the linkage region of speech and language disorders, and a rare translocation in a dyslexic individual that was brought to our attention, we conducted a series of studies on the properties of CYP19A1 as a candidate gene for dyslexia and related conditions.

The aromatase enzyme is a member of the cytochrome P450 super family, and it serves several key functions:

• it catalyzes the conversion of androgens into estrogens; 
• during early mammalian development it controls the differentiation of specific brain areas (e.g. local estrogen synthesis in the hippocampus regulates synaptic plasticity and axonal growth); 
• it is involved in sexual differentiation of the brain; 
• and in songbirds and teleost fishes, it regulates vocalization. 

Our results suggest that variations in CYP19A1 are associated with dyslexia as a categorical trait and with quantitative measures of language and speech, such as reading, vocabulary, phonological processing and oral motor skills.

Variations near the vicinity of its brain promoter region altered transcription factor binding, suggesting a regulatory role in CYP19A1 expression. CYP19A1 expression in human brain correlated with the expression of dyslexia susceptibility genes such as DYX1C1 and ROBO1.

Aromatase-deficient mice displayed increased cortical neuronal density and occasional cortical heterotopias, also observed in Robo1−/− mice and human dyslexic brains, respectively.

An aromatase inhibitor reduced dendritic growth in cultured rat neurons. From this broad set of evidence, we propose CYP19A1 as a candidate gene for human cognitive functions implicated in reading, speech and language.

Download the Paper PDF here: CYP19A1 Gene

Read the Full Text Preview at SpringerLink

Scientists discover gene which causes FGD, rare disease in babies

A rare disease which often first presents in newborn babies has been traced to a novel genetic defect, scientists at Queen Mary, University of London have found.

 

The research, published online in Nature Genetics (27 May) discovered 20 distinct mutations in a specific gene found in patients with the rare adrenal disease, Familial Glucocorticoid Deficiency (FGD).

The potentially fatal disease means affected children are unable to produce a hormone called cortisol which is essential for the body to cope with stress.

Lead researcher Dr Lou Metherell*, endocrine geneticist at Queen Mary, University of London, said: "People who inherit this disease are unable to cope with physical stress.

For example, the normal response to infection or traumatic injury is to produce cortisol supporting the metabolic response to the event. Patients with FGD cannot do this and may die if untreated.

"We found 20 distinct defects in the antioxidant gene nicotinamide nucleotide transhydogenase (NNT) in patients from all over the world who suffer from FGD."

The researchers, which include Eirini Meimaridou and Professor Adrian Clark, also at Queen Mary in the William Harvey Research Institute, had previously found defects in four genes present in this disease.

The new research uncovered mutations in NNT, an antioxidant gene, which provides a new mechanism for this adrenal disease.

"Patients with this form of FGD exhibit oxidative stress (OS) in the adrenal, a process which is involved in other diseases such as neurodegenerative conditions, cancer, stroke, diabetes and cardiac dysfunction," Professor Clark said.

"If we can discover how the OS causes its effect then this might give us clues to the mechanism in other diseases like those listed above and it may then be possible to use appropriate drugs to reduce or prevent it."

More information: "Mutations in NNT encoding nicotinamide nucleotide transhydrogenase cause familial glucocorticoid deficiency" was published online in Nature Genetics on 27 May 2012.

Journal reference: Nature Genetics

Provided by Queen Mary, University of London

A Step Closer to Resolving Birth Defects

Scientists have made a landmark discovery that could help women minimize or even avoid the risk of having a baby born with congenital birth defects. The study is published April 5 in the international journal Cell.

The scientists, from universities in Australia, Japan, Canada and the United States, including Arizona State University, show for the first time how “nature” and “nurture” interact to increase the severity and likelihood of developing birth defects, including abnormalities in the heart, kidneys, brain, limbs and cranio‐facial regions (cleft palate).

They show how hypoxia, or a period of low oxygen during pregnancy, combined with a genetic risk factor of having only one functioning copy of a gene, dramatically increases the chances of a baby being born with congenital scoliosis, a malformation of the spine that affects around 1 in 1,000.

Sally Dunwoodie, head of the Embryology Laboratory at the Victor Chang Cardiac Research Institute in Sydney, Australia, a professor at the University of New South Wales and the senior author on the study, says the findings take us a step closer to understanding why some people in families develop diseases and others don’t, and, importantly, simple strategies that mothers could adopt to help prevent such defects occurring.

“We’ve long suspected that it is genes or our environment that cause birth defects, but up until now, the majority of these have been largely unknown,” says Dunwoodie. “This is the first time anyone in the world has shown that both ‘nature’ and ‘nurture’, in combination, are molecularly responsible for causing many birth defects.”

“This research is hugely exciting and will help us to genetically diagnose a whole range of birth defects, and give advice to women on how and when to avoid certain activities when pregnant,” says Dunwoodie. “We hope it will eventually lead to the development of therapeutics to stop these defects occurring in the first place.”

Hypoxia during pregnancy can be caused by a range of circumstances including poorly controlled sugar levels in diabetics, smoking, high altitude, prescription and recreational drug‐use, anemia or a poorly functioning placenta.

“Just as genetic studies of selected families led to the discovery of genes causing breast cancer, this study of the genetics and development of congenital scoliosis will lead to breakthroughs in finding the factors that cause scoliosis, a disorder affecting up to 3 percent of the general population,” says co-author Kenro Kusumi, an associate professor in the School of Life Sciences in ASU’s College of Liberal Arts and Sciences.

One of the largest genetic studies focused on congenital scoliosis was led by Kusumi’s group. Together with clinical collaborators in Philadelphia and Toronto, the group identified the first case of a patient with congenital scoliosis due to having a single defective copy of the HES7 gene. Previous studies in mice had established that disruptions in this gene could lead to spinal defects, and loss of both copies of this gene had been found in severe cases of spinal deformities. The type of defect found in the patient in the ASU study was shown by Dunwoodie’s group to clearly affect the ability of the protein to function normally. This finding meant that having just one, instead of two functioning copies of a known gene from either mother or father, was a major risk factor for causing the abnormal formation of vertebrae in embryonic development.

Dunwoodie’s group then went on to test the genetic risk factor in a mouse model combined with an environmental insult in the form of hypoxia. Surprisingly, they found a marked increase in spinal abnormalities in the offspring, when the mothers were exposed to only 8 hours of low oxygen during an entire 21‐day pregnancy.

“We found that the combination of the genetic risk as well as exposure to low oxygen, resulted in our subjects being up to 10 times more likely to develop congenital scoliosis, than those that only had the genetic risk factor,” says Dunwoodie.

“What this brief period of low oxygen essentially did was disrupt the pathway responsible for development of the spine, and we know that the same pathway is used in the development of limbs and many organs, including the heart, kidneys, brain and cranio‐facial region,” adds Dunwoodie.

Bob Graham, a professor and executive director of the cardiac research institute, says around 25 percent of patients with congenital scoliosis also have some form of congenital heart defect, indicating that a single environmental ‘insult’ such as hypoxia, can potentially affect the development of more than one organ in the body.

“This study provides a new paradigm for the interaction between our genes and environment, and may account for a lot of diseases that we haven’t understood before, such as many different forms of congenital heart disease, and conditions like hair‐lip or cleft palate,” says Graham.

Kusumi points to a recent genetic study of over 50,000 identical twins that emphasizes that the risk of developing disease arises from the environment acting together with a person’s unique genome. “For scoliosis, our study highlights how environmental conditions, such as lack of oxygen reaching the developing embryo, could interact uniquely with each individual’s genetic differences to increase the risk of birth defects,” said Kenro.

“It may not necessarily be a lack of oxygen that allows the underlying gene defect to be revealed, it could be a lot of other environmental factors, such as anemia or lack of folate. But the message is, if you have family history of disease or you know you have a defective gene, mums need to be extra careful during pregnancy,” adds Graham.

The team of researchers has begun working on similar studies in congenital heart defects, which affect around 1 in every 100 babies born world-wide every year.

Prosopagnosia - Face Blidness

Prosopagnosia is a disorder of face perception where the ability to recognize faces is impaired, while the ability to recognize other objects may be relatively intact.

The term originally referred to a condition following acute brain damage, but a congenital form of the disorder has been proposed, which may be inherited by about 2.5% of the population.

The specific brain area usually associated with prosopagnosia is the fusiform gyrus.

Few successful therapies have so far been developed for affected people, although individuals often learn to use 'piecemeal' or 'feature by feature' recognition strategies.

This may involve secondary clues such as clothing, gait, hair colour, body shape, and voice. Because the face seems to function as an important identifying feature in memory, it can also be difficult for people with this condition to keep track of information about people, and socialize normally with others.

Some also use the term prosophenosia, which refers to the inability to recognize faces following extensive damage of both occipital and temporal lobes.

Children with Prosopagnosia
Developmental prosopagnosia can be a difficult thing for a child to both understand and cope with. Many adults with developmental prosopagnosia report for a long time they had no idea that they had a deficit in face processing, unaware that others could distinguish people solely on facial differences.

Children with prosopagnosia can be hard to find. They may just appear to be very shy or slightly odd due to their inabilities to recognise faces.

Children with prosopagnosia may have a hard time making friends, as they may not recognize their classmates. They often make friends with children with other distinguishing features.

Children with prosopagnosia may also have difficulties following the plots of television shows and movies, as they have trouble recognizing the different characters.

They tend to gravitate towards cartoons, where the characters always wear the same thing and have other distinguishing features.

Prosopagnosiac children may also have a hard time telling family members apart or recognizing people out of context (i.e. the teacher in a grocery store).

Additionally, those children with prosopagnosia can have a difficult time with the public school system, as many school professionals are not well versed in prosopagnosia, if they are aware of the disorder at all.

Resources
Resources to help parents and professionals cope with prosopagnosia in children are also being developed, such as Understanding Facial Recognition Disorders in Children by Nancy L. Mindick

Oliver Sacks, famous neuroscientist, author of many books including The Man Who Mistook His Wife for a Hat; although he knew what prosopagnosia was and had studied it, he did not realise he had it until people became shocked that he confused one of his brothers with the other and then, discussing it with family members, learned that a number of them had similar difficulties with face.

Dame Jane Goodall, British primatologist, ethologist, and anthropologist, best known for her 45-year study of social and family interactions of wild chimpanzees.

Listen to Jane describe her condition and how it's affected her life:

Autism: Researchers find another piece of the puzzle

Autism spectrum disorders (ASDs) have a complex inheritance pattern. Despite researchers having identified rare variants in synaptic proteins in patients with ASD, little work has been carried out to determine the effect at the synapse and their interactions with other genetic variations, until now.

A European team of researchers has confirmed that synaptic mutations heightens the risk of ASD.

The study, presented in the journal PLoS Genetics, was funded in part by the EUHFAUTISM ('European high-functioning autism network: translational research in a phenotypically well characterised sample') project, a Neuron-ERA-NET funded under the EU's Seventh Framework Programme (FP7) to the tune of almost EUR 370,000.

Researchers led by the Institut Pasteur in France combined genetic and neurobiological approaches to determine how ASD risk increases. They also found how modifier genes influence these disorders.

ASDs are a heterogeneous group of neurodevelopmental disorders with a complex inheritance pattern characterised by impairments in social interaction and communication. Repetitive behaviour also restricts them.

According to the researchers, ASDs emerge before the age of three years and affect 1% of children. More boys than girls have a higher risk of being affected by ASD.

The researchers say a number of genes that play a role in ASD have been identified in patients with ASD. However, researchers have only recently begun learning about their effects on neuronal functions and their interaction with other genetic variations.

'The genetic causes of ASD are diverse, but the main category of genes associated with the disorder is related to the development and function of neuronal circuits,' the authors write.

 'Mutations of genes coding for synaptic cell adhesion molecules and scaffolding proteins, such as neuroligins (NLGNs), neurexins (NRXNs) and SHANK, have been recurrently reported in patients with ASD. These proteins play a crucial role in the formation and stabilisation of synapses, as well as in synaptic homeostasis.

'SHANK2 and SHANK3 code for scaffolding proteins located in the postsynaptic density (PSD) of glutamatergic synapses. Deletions of ProSAP2/SHANK3 at chromosome 22q13 are one of the major genetic abnormalities in neurodevelopmental disorders, and mutations of ProSAP2/SHANK3 have been identified in patients with ASD, intellectual disability (ID) and schizophrenia. Mutations of ProSAP1/SHANK2 have also recently been reported in both ASD and ID. The difference in clinical outcome of mutation carriers has been attributed to the presence of still uncharacterised additional genetic, epigenetic and/or environmental factors.'

Commenting on the significance of the findings, the Institut Pasteur's Thomas Bourgeron says they emphasise the importance of a synaptic gene dysfunction in ASD, and they underline a role for modifier genes confirming 'a multiple hit model for ASD. A better knowledge of these genetic interactions will be necessary to understand the complex inheritance pattern of ASD'.

For more information, please visit:

Institut Pasteur: http://www.pasteur.fr/ip/easysite/pasteur/fr

PLoS Genetics: http://www.plosgenetics.org/home.action

Babies have ‘intuitive physics’ knowledge at birth?

A US Northwestern University study has found that the evidence for intuitive physics occurs in infants as young as two months – the earliest age at which testing can occur.

Intuitive physics includes skills that adults use all the time. For example, when a glass of milk falls off the table, a person might try to catch the cup, but they are not likely to try to catch the milk that spills out.

The person doesn’t have to consciously think about what to do because the brain processes the information and the person simply reacts.

The majority of an adult’s everyday interactions with the world are automatic, and researchers believe infants have the same ability to form expectations, predicting the behaviour of objects and substances with which they interact.

But the world is not made up of objects alone, and Northwestern researchers looked at whether babies can distinguish between objects in their different forms i.e. one's that can be held, touched or thrown, versus substances such as gas, liquids that can flow and may be drinkable.

According to a review of literature, infants show an understanding that unsupported objects will fall and that hidden objects do not cease to exist. Scientific testing also has shown that by five months, infants have developed the expectation that non-cohesive substances like a gas, sand or water are not solid.

“I think liquid is the best example of a non object that you interact with — a baby has to drink liquid every single day,” said lead author Susan J. Hespos, associate professor of psychology at Northwestern’s Weinberg College of Arts and Sciences.

“It’s a universal experience with milk or water. We did studies on whether babies expected water to pour or tumble from an upended cup.

By five months of age, babies expect both water and sand to pour, so we have clear evidence that this type of physical knowledge is available early in development.”

While the intuitive physics knowledge is believed to be present at birth, co-author Kristy van Marle, assistant professor of psychology at the University of Missouri, believes parents can assist skill development through normal interaction, such as playing and talking with the child and encouraging him or her to interact with objects.

“Natural interaction with the child, such as talking to him or her, playing peek-a-boo and allowing him or her to handle safe objects, is the best method for child development,” van Marle said.

“Natural interaction with the parent and objects in the world gives the child all the input that evolution has prepared the child to seek, accept and use to develop intuitive physics.”

Read more on 'Intuitive Physics' in this paper by McCloskey 

Also you can read another, older (2001), paper; "Are 'intuitive physics' and
'intuitive psychology' independent? - Testing children with Asperger Syndrome

Timothy Syndrome: Brain finding sheds light on autism

Cells taken from people with a rare syndrome linked to autism could help explain the origins of the condition, scientists suggest.

The Stanford University team turned skin cells from people with "Timothy syndrome" into fully-fledged brain cells.

The abnormal activity found in these cells could be partially corrected using an experimental drug, Nature Medicine reports.

UK researchers warned the findings might not apply to everyone with autism.

Compared with the hundreds of thousands of people worldwide thought to show characteristics of autism, "Timothy syndrome" is vanishingly rare, affecting an estimated 20 people across the planet.

People who have the syndrome frequently display autistic behaviour, such as problems with social development and communication.

Because it is caused by a single gene defect rather than a combination of small genetic flaws, each making a tiny contribution, it presents a useful target for scientists looking to examine what goes wrong in the developing brain of a child with autism.

Ready for work

The US researchers used a technique developed recently to generate brain cells called neurons from only a sample of the patient's skin.

This allowed them to examine their development in the laboratory, and even use them to test out possible treatments.

They found obvious differences between neurons grown from Timothy syndrome patients, and those from healthy "control" subjects.

The healthy neurons developed into different subtypes, ready for work in different regions of the brain.

In contrast, the proportion of neurons developing into each subtype was different in the Timothy syndrome samples - more were equipped to work in the upper part of the cerebral cortex, and fewer in the lower part.

This meant there were fewer neurons equipped to work in a part of the brain called the corpus callosum, which has the role of helping the left and right "hemispheres" of the brain communicate.

These differences echoed those already observed in mice specially bred with the Timothy syndrome genetic fault.

In addition, the neurons were making too much of a particular body chemical linked to the manufacture of dopamine and norepinephrine, which play a significant role in sensory processing and social behaviour.

Dr Ricardo Dolmetsch, who led the study, said that the abnormalities found tallied with other evidence that autism was due in part to poor communication between different parts of the brain.

The team managed to reduce significantly the number of these malfunctioning neurons by adding a drug as they developed.

This, they said, meant it might be possible one day to treat this defect in a real patient, although the drug used was not currently suitable for children due to side-effects.

The National Autistic Society gave a cautious welcome to findings, but warned that they did not necessarily offer insights into every form of autism.

Researcher Georgina Gomez said: "Timothy syndrome is only one form of autism and so these findings only give a very limited picture of what might cause the condition.

"More work would need to be done to substantiate this particular piece of research."

Notes From a Dragon Mom - A child with Tay-Sachs, a rare genetic disorder

We found this very moving and interesting article in the NY Times. It's from Emily Rapp is the author of “Poster Child: A Memoir” She is also a professor of creative writing at the Santa Fe University of Art and Design:


MY son, Ronan, looks at me and raises one eyebrow. His eyes are bright and focused. Ronan means “little seal” in Irish and it suits him.

I want to stop here, before the dreadful hitch: my son is 18 months old and will likely die before his third birthday. Ronan was born with Tay-Sachs, a rare genetic disorder.

He is slowly regressing into a vegetative state. He’ll become paralysed, experience seizures, lose all of his senses before he dies. There is no treatment and no cure.

How do you parent without a net, without a future, knowing that you will lose your child, bit by torturous bit?

Depressing? Sure. But not without wisdom, not without a profound understanding of the human experience or without hard-won lessons, forged through grief and helplessness and deeply committed love about how to be not just a mother or a father but how to be human.

Parenting advice is, by its nature, future-directed. I know. I read all the parenting magazines. During my pregnancy, I devoured every parenting guide I could find.

My husband and I thought about a lot of questions they raised: will breast-feeding enhance his brain function? Will music class improve his cognitive skills? Will the right preschool help him get into the right college? I made lists. I planned and plotted and hoped. Future, future, future.

We never thought about how we might parent a child for whom there is no future. The prenatal test I took for Tay-Sachs was negative; our genetic counselor didn’t think I needed the test.

I’m not Jewish and Tay-Sachs is thought to be a greater risk among Ashkenazi Jews. Being somewhat obsessive about such matters, I had it done anyway, twice. Both times the results were negative.

Our parenting plans, our lists, the advice I read before Ronan’s birth make little sense now. No matter what we do for Ronan, choose organic or non-organic food; cloth diapers or disposable; attachment parenting or sleep training, he will die. All the decisions that once mattered so much, don’t.

All parents want their children to prosper, to matter. We enroll our children in music class or take them to Mommy and Me swim class because we hope they will manifest some fabulous talent that will set them and therefore us, the proud parents, apart.

Traditional parenting naturally presumes a future where the child outlives the parent and ideally becomes successful, perhaps even achieves something spectacular.

Amy Chua’s “Battle Hymn of the Tiger Mother” is only the latest handbook for parents hoping to guide their children along this path. It’s animated by the idea that good, careful investments in your children will pay off in the form of happy endings, rich futures.

I have abandoned the future, and with it any visions of Ronan’s scoring a perfect SAT or sprinting across a stage with a Harvard diploma in his hand.

We’re not waiting for Ronan to make us proud. We don’t expect future returns on our investment.

We’ve chucked the graphs of developmental milestones and we avoid parenting magazines at the pediatrician’s office. Ronan has given us a terrible freedom from expectations, a magical world where there are no goals, no prizes to win, no outcomes to monitor, discuss, compare.

The day-to-day is often peaceful, even blissful. This was my day with my son: cuddling, feedings, naps.

He can watch television if he wants to; he can have pudding and cheesecake for every meal.

We are a very permissive household. We do our best for our kid, feed him fresh food, brush his teeth, make sure he’s clean and warm and well rested and, healthy?

Well, no. The only task here is to love, and we tell him we love him, not caring that he doesn’t understand the words. We encourage him to do what he can, though unlike us he is without ego or ambition.

Ronan won’t prosper or succeed in the way we have come to understand this term in our culture; he will never walk or say “Mama,” and I will never be a tiger mom.

The mothers and fathers of terminally ill children are something else entirely. Our goals are simple and terrible: to help our children live with minimal discomfort and maximum dignity.

We will not launch our children into a bright and promising future, but see them into early graves. We will prepare to lose them and then, impossibly, to live on after that gut wrenching loss.

This requires a new ferocity, a new way of thinking, a new animal. We are dragon parents: fierce and loyal and loving as hell.

Our experiences have taught us how to parent for the here and now, for the sake of parenting, for the humanity implicit in the act itself, though this runs counter to traditional wisdom and advice.

To read the full story follow this link Notes From a Dragon Mom - NYTimes.com

Deletion of a 27-gene cluster on chromosome 16, causes Autism-like features

Scientists at Cold Spring Harbour Laboratory (CSHL) have discovered that one of the most common genetic alterations in autism, deletion of a 27-gene cluster on chromosome 16, causes autism-like features.

By generating mouse models of autism using a technique known as chromosome engineering, CSHL Professor Alea Mills and colleagues provide the first functional evidence that inheriting fewer copies of these genes leads to features resembling those used to diagnose children with autism.

The study appears in the Proceedings of the National Academy of Sciences in the early online edition during the week of October 3.

"Children normally inherit one copy of a gene from each parent. We had the tools to see whether copy number changes found in kids with autism were causing the syndrome," explains Mills. In 2007, Professor Michael Wigler, also at CSHL, revealed that some children with autism have a small deletion on chromosome 16, affecting 27 genes in a region of our genomes referred to as 16p11.2.

The deletion, which causes children to inherit only a single copy of the 27-gene cluster is one of the most common copy number variations (CNVs) associated with autism.

"The idea that this deletion might be causing autism was exciting," says Mills. "So we asked whether clipping out the same set of genes in mice would have any effect."

After engineering mice that had a chromosome defect corresponding to the human 16p11.2 deletion found in autism, Mills and her team analyzed these models for a variety of behaviors, as the clinical features of autism often vary widely from patient to patient, even within the same family.

"Mice with the deletion acted completely different from normal mice," explains Guy Horev, a Postdoctoral Fellow in the Mills laboratory and first author of the study. These mice had a number of behaviors characteristic of autism: hyperactivity, difficulty adapting to a new environment, sleeping deficits, and restricted, repetitive behaviors.

Interestingly, mice that had been engineered to carry an extra copy, or duplication, of the 16p11.2 region did not have these characteristics, but instead, had the reciprocal behaviors. For each behavior, the deletion had a more dire consequence than the duplication, indicating that gene loss was more severe. This might explain why 16p11.2 duplications are detected much more frequently than deletions within the human population, and why patients with 16p11.2 deletions tend to be diagnosed earlier than those with duplications.

The mouse models also revealed a potential link between 16p11.2 deletion and survival, as about half the mice died following birth. Whether these findings extend to the human population might be answered by future studies that investigate the link between this deletion and unexplained cases of infant death.

The researchers also used MRI to identify specific regions of the brain that were altered in the autism models, revealing that eight different parts of the brain were affected. The group is now working to identify which gene or group of genes among the 27 that are located within the deleted region is responsible for the behaviors and brain alterations observed.

"Alea Mills has created a valuable resource for everyone engaged in autism research. The technical skill is extraordinary in creating mouse models bearing a human genetic variant that has been associated with autism," says Dr. Gerald Fischbach, Director of Life Sciences and Simons Foundation Autism Research Initiative (SFARI).

Autism risks amended for siblings - higher than thought

A new study suggests nearly one in five children with an autistic older sibling will develop the disorder too — a rate much higher than previously thought.

Researchers followed 664 infants who had at least one older brother or sister with autism. Overall, 132 infants or about 19 percent ended up with an autism diagnosis, too, by their third birthdays. Previous smaller or less diverse studies reported a prevalence of between 3 percent and 14 percent.

"We were all a bit surprised and taken aback about how high it is," said lead author Sally Ozonoff, a psychiatry and behavioral sciences professor with the Mind Institute at the University of California at Davis.

The highest rates were in infants who had at least two older siblings with autism — 32 percent of them also developed autism. Also, among boys with autistic siblings — 26 percent developed autism versus 9 percent of girls. Autism is already known to be more common in boys.

The study involved 12 U.S. and Canadian sites and was published online Monday in Pediatrics. Earlier studies were more local or involved fewer sites.

Ozonoff said parents of autistic children often ask her, "How likely am I to have another child" with autism? She said her study provides a more up-to-date answer.

However, Ozonoff noted that 80 percent of siblings studied did not develop autism, and that the prevalence rate was an average. It may be different for each family, depending on other risk factors they may face.

Autism has no known cause but experts believe that genetics and external influences are involved. Research is examining whether these could include infections, pollution and other non-inherited problems. Ozonoff noted that siblings often are exposed to similar outside influences, which could partly explain the study results.

Infants in the study were enrolled before they showed any signs of autism, such as poor eye contact and little social interaction.

The study is an important addition to autism research and "has critical implications for families who are deciding whether they'll have another child," said Catherine Lord, director of the Institute for Brain Development at New York-Presbyterian/Weill Cornell Medical Center. Lord was not involved in the study.

Kathleen Lanese of Kings Park, N.Y., says having one son with autism didn't make her think twice about trying to have another child, even though she knew there was a chance the second would be affected, too.

"We wanted another child and we were going to take whoever we got," said Lanese, who was not involved in the study. Still, when her younger son was a baby, she says she "watched him like a hawk" for autism signs. He was diagnosed with autism at 16 months, earlier than her older boy.

Ozonoff said the study should prompt families and their children's doctors to be vigilant with infants whose older siblings have autism. Early diagnosis is important because experts say behavioral treatment has the best chance of working if started early.

"Pediatricians need to listen and make a very focused plan for how to monitor those things, rather than taking a wait-and-see attitude" toward children with autistic siblings, Ozonoff said.

Alycia Halladay, a research director at the advocacy group Autism Speaks, said the study provides a more robust, accurate prevalence estimate than previous studies, and strengthens the idea that family history is a risk factor.

Her group, the National Institutes of Health and the Canadian Institute for Health Research are among those who paid for the study.

___

Online:

American Academy of Pediatrics: http://www.aap.org

National Institutes of Health: http://health.nih.gov/topic/Autism

Primary symptoms of psychosis may be evident in 12-year-olds

Children normally experience flights of fancy, including imaginary friends and conversations with stuffed animals, but some of them are also having hallucinations and delusions which might be the early signs of psychosis.

A study of British 12-year-olds that asked whether they had ever seen things or heard voices that weren't really there, and then asked careful follow-up questions, has found that nearly 6 percent may be showing at least one definite symptom of psychosis.

The children who exhibited these symptoms had many of the same risk factors that are known to correlate with adult schizophrenia, including genetic, social, neurodevelopmental, home-rearing and behavioral risks.

"We don't want to be unduly alarmist, but this is also not something to dismiss," said co-author Terrie Moffitt, the Knut Schmidt Nielsen professor of psychology and neuroscience and psychiatry & behavioral sciences at Duke University. The study appears in the April issue of Archives of General Psychiatry.

The children were participants in the long-term Environmental Risk Longitudinal Twin Study in Britain, which includes 2,232 children who have been tracked since age 5 and reassessed at 7, 10 and 12.

The British study is an outgrowth of research that the same group did earlier with a long-term cohort in Dunedin, New Zealand. At age 11, those children were asked about psychotic symptoms, but the researchers waited 15 years to see how, as adults, their symptoms matched what they reported at 11. By age 26, half of the people who self-reported symptoms at age 11 were found to be psychotic as adults.

"It looks like a non-trivial minority of children report these symptoms," said co-author Avshalom Caspi, the Edward M. Arnett professor of psychology and neuroscience and psychiatry & behavioral sciences at Duke.

The findings provide more clues to the development of schizophrenia, but don't solve any questions by themselves, said co-author Richard Keefe, director of the schizophrenia research group in the department of psychiatry and behavioral sciences at Duke.

Schizophrenia often goes undetected until adolescence, when the first overt symptoms -- antisocial behavior, self-harm, delusions -- begin to manifest in an obvious way. But nobody knows whether the disease is triggered by the process of adolescence itself, or brain development or hormone changes. "It's my impression that all of those things interact," Keefe said.

Psychotic symptoms in childhood also can be a marker of impaired developmental processes, and are something caregivers should look for, Moffitt said. "There is not much you can do except monitoring and surveillance," Moffitt said. "But we feel we should be alerting clinicians that there's a minority to pay attention to."

While the incidence of psychotic symptoms in this study was around 5 or 6 percent, the adult incidence of schizophrenia is believed to be about 1 percent, Keefe added. There are some recent findings however, that many more people experience hallucinations and delusions without being diagnosed as psychotic, he said.

The research was supported by the U.S. National Institutes of Health, UK Medical Research Council, The National Alliance of Research on Schizophrenia and Depression, the Health Research Board of Ireland and the William T. Grant Foundation.

Etiological and Clinical Features of Childhood Psychotic Symptoms, Guilherme Polanczyk et al, Archives of General Psychiatry, April 2010 http://archpsyc.ama-assn.org/cgi/content/full/67/4/328

Link: http://www.duke.edu/

Could Autism and Schizophrenia be Genetic?

Autism and schizophrenia may be two sides of the same coin, suggests a review of genetic data associated with the conditions. The finding could help design complementary treatments for the two disorders.

Though autism was originally described as a form of schizophrenia a century ago, evidence for a link has remained equivocal. One theory puts the conditions at opposite ends of a developmental spectrum.

To investigate, Bernard Crespi, an evolutionary biologist at Simon Fraser University in Vancouver, Canada, and colleagues gathered data on all known genetic variants associated with each condition, then looked for patterns of co-occurrence.

The researchers found four regions in the genome which dramatically affect the risk of autism or schizophrenia. Called "copy-number variants", these are stretches of DNA with seemingly accidental duplications or deletions. Crespi's team found that the presence of a particular variant – a duplication, say – was often associated with autism while the opposite variation – a deletion of the genetic material – was linked to schizophrenia.

The results fit with other evidence that autism may be caused by overdevelopment of specific brain regions and schizophrenia by underdevelopment, says Crespi.

If they are indeed opposites, work on one disorder may inform work on its counterpart, he says.

Journal reference: Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.0906080106