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.

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Listen up: Does Abnormality in auditory processing underlie dyslexia

People with dyslexia often struggle with the ability to accurately decode and identify what they read.

Although disrupted processing of speech sounds has been implicated in the underlying pathology of dyslexia, the basis of this disruption and how it interferes with reading comprehension has not been fully explained.

Now, new research published by Cell Press in the December 22 issue of the journal Neuron finds that a specific abnormality in the processing of auditory signals accounts for the main symptoms of dyslexia.

"It is widely agreed that for a majority of dyslexic children, the main cause is related to a deficit in the processing of speech sounds," explains senior study author, Dr. Anne-Lise Giraud and Franck Ramus from the Ecole Normale Supérieure in Paris, France.

"It is also well established that there are three main symptoms of this deficit:

• difficulty paying attention to individual speech sounds, 
• a limited ability to repeat a list of pseudowords or numbers, and 
• a slow performance when asked to name a series of pictures, colors, or numbers as quickly as possible.

However, the underlying basis of these symptoms has not been elucidated."

Dr. Giraud and colleagues examined whether an abnormality in the early steps of auditory processing in the brain, called "sampling," is linked with dyslexia by focusing on the idea that an anomaly in the initial processing of phonemes, the smallest units of sound that can be used to make a word, might have a direct impact on the processing of speech.

The researchers found that typical brain processing of auditory rhythms associated with phonemes was disrupted in the left auditory cortex of dyslexics and that this deficit correlated with measures of speech sound processing.

Further, dyslexics exhibited an enhanced response to high-frequency rhythms that indirectly interfered with verbal memory.

It is possible that this "oversampling" might result in a distortion of the representation of speech sounds.

"Our results suggest that the left auditory cortex of dyslexic people may be less responsive to modulations at very specific frequencies that are optimal for analysis of speech sounds and overly responsive to higher frequencies, which is potentially detrimental to their verbal short-term memory abilities," concludes Dr. Giraud.

"Taken together, our data suggest that the auditory cortex of dyslexic individuals is less fine-tuned to the specific needs of speech processing."