Noonan syndrome: Father's age affects offspring

In a new paper, USC Dornsife molecular and computational biologists Norman Arnheim and Peter Calabrese and their team found that the longer a man waits to have children, the greater the chance of having a child with Noonan syndrome.

Norman Arnheim

Scientists in USC Dornsife have unlocked the mystery of why new cases of the genetic disease Noonan syndrome are so common—a mutation that causes the disease disproportionately increases a normal father's production of sperm carrying the disease trait.

When the mutation arises in a normal sperm stem cell, it makes that cell more likely to reproduce itself than stem cells lacking the mutation.

The father then is more likely to have an affected child because more mutant stem cells result in more mutant sperm.

The longer the man waits to have children, the greater the chance of having a child with Noonan syndrome, which is among the most common genetic diseases with a simple inheritance pattern.

About one of every 4,000 live births is a child with a new disease mutation. The disease can cause craniofacial abnormalities, short stature, heart defects, intellectual disability and sometimes blood cancers.

Peter Calabrese

By examining the testes of 15 unaffected men, a team led by USC Dornsife molecular and computational biologists Norman Arnheim and Peter Calabrese found that the new mutations were highly clustered in the testis and that the overall proportion of mutated stem cells increased with age.

Their computational analysis indicated that the mutation gave a selective edge over nonmutated cells.

"There is competition between stem cells with and without the mutation in each individual testis," said Arnheim, who holds a joint at the Keck School of Medicine of USC.

"But what is also unusual in this case is that the mutation which confers the advantage to testis stem cells is disadvantageous to any offspring that inherits it."

The new findings also suggested an important new molecular mechanism to explain how certain genetic disease mutations can alter sperm stem cell function leading to exceptionally high frequencies of new cases every generation.

The Arnheim and Calabrese team paper detailing their research was published on June 6 in The American Journal of Human Genetics.

Knowing the Gender of Unborn Child Helps Fathers Bond with Offspring

Dads who find out the sex of their unborn child and give him or her a name may find it easier to connect emotionally with their baby, a study conducted at the University of Birmingham has found.

The report, entitled "The Moral Habitus of Fatherhood: A Study of How Men Negotiate the Moral Demands of Becoming a Father," funded by the Economic and Social Research Council, looked at men's experiences of, and feelings about, becoming a father and mapped their journeys from the discovery of the pregnancy to the early months of fatherhood.

Jonathan Ives

Dr Jonathan Ives, a senior lecturer in the centre for Medicine, Ethics, Society and History at the University of Birmingham, who carried out the research, said: "Serious consideration needs to be given to how men can be empowered to become the fathers they want to be.

"Healthcare workers who are involved in this process need to engage with men's views on what it is to be a good man, a good partner, and a good father and help them achieve an appropriate balance between their own needs and interests and those of their partner and future children."

The study found that some men's understanding of what it means to be a good man and/or a good partner could act as a barrier to being drawn into, or actively seeking involvement in antenatal or postnatal consultation, but that "this is not necessarily demonstrative of a lack of commitment to fatherhood, but merely a different construction of the fatherhood role in that context".

"Helping men effect an 'active transformation into positive fatherhood' may require helping them to reconcile their moral sense of how they ought to act as a partner and as a man, with how they need to act as a father and a father-to-be," the report states.

"Encouraging fathers to become actively involved, and drawing them in, may require more than making them feel welcome and creating space for them to talk, but also giving them explicit permission to become actively involved."

The research found that scans helped to make their partner's pregnancy more real for men but "it was discovering the gender of their child, and giving him/her a name that tended to enable men to feel emotionally connected, because it allowed them to think of the unborn child as a person whom one can father, and with whom a relationship could be developed and a future imagined".

Dr Ives followed 11 men over a period of 9 months, from the first scan to 8 weeks after the birth of their child. The ages of participants ranged from 22 to 58.

Jason Cole, one of the dads who took part in the research, said: "I really wanted to know the gender of our first child.

My partner wasn't fussed. She was happy either way but I really wanted to know. I don't know why. As soon as we found out she was a girl, from about 20 weeks, we named her Molly and I think it did help me prepare for her and connect with her once she was born."

Mr Cole, who lives in Devon, is happy to discuss his experiences with the press. He and his partner are now expecting their second child – also a girl.

More information: www.birmingham.ac.… oject-1.aspx