THE MUTATION OCCURRED IN SPERM CELLS OF A FATHER WHO DOES NOT HAVE AUTISM BOTH OF HIS DAUGHERS ARE AUTISTIC, THEY INHERITED A CHROMOSOME WITH MISSING

DNA


Researchers Learn More About Genetic Mutation Linked To Autism
I AM NOT CONVINCED THAT THIS MUTATION IS A MOSAICISM, HOW OLD WAS THE FATHER OF THESE DAUGHTERS WHEN HIS FIRST CHILD WAS BORN? MIGHT THE DELETION BE DUE TO A STRUCTURAL CHROMOSOMAL ABERRATION DUE TO ADVANCING PATERNAL AGE?

By the Press-Citizen


From the University of Iowa Health News Service
University of Iowa researchers have learned more about a genetic mutation that contributes to autism. The mutation occurred in sperm cells of a father, who does not have autism, but passed the condition on to two of his children.

The investigators now know more about how the mutation causes problems with a specific gene and are testing for additional mutations of the same gene in other people with autism. Dr. Thomas Wassink, associate professor of psychiatry in UI’s Carver Col-lege of Medicine, is presenting the findings today at the annual International Meeting for Autism Research in Seattle.

Earlier this year, UI researchers and collaborators were part of an international team that identified, among other findings, de-letions in a gene called neurexin 1, which caused the two cases of autism in one family. The UI researchers and collaborators in-cluded Wassink; Dr. Val Sheffield, UI professor of pediatrics and a Howard Hughes Medical Investigator; Kacie Meyer, a graduate student in Wassink’s laboratory; and former UI investigator Dr. Joseph Piven, now professor of psychiatry at the University of North Carolina and director of the UNC Neurodevelopmental Disorders Research Center.

"Genes with the most compelling evidence of causing autism appear to be components of a specific kind of neuronal connec-tion, or synapse, called the glutamate synapse. The gene neurexin 1 was the fourth of these genes to be identified, and it is a scien-tifically interesting mutation because it wasn’t found in either of the parents, who do not have autism," Wassink said.

Instead, the mutation is a germline mosaic — meaning the deletion occurred only in the father’s sperm cells when he himself was in gestation. As result, the father did not have autism, but his two children, both daughters, inherited from him a chromosome that was missing a small piece of DNA that contained neurexin 1. The daughters now have autism.

Because of this missing DNA, certain proteins cannot form that normally contribute to glutamate synapses and, by extension, normal development.

"Now, using this information, we can look in a very detailed way at this gene in other families and begin to understand what happens when this protein that is normally active in the brain is missing," Wassink said.

Knowing more about how the deletions function could eventually lead to the development of diagnostic and therapeutic tools for autism, a complex brain disorder that inhibits a person’s ability to communicate and develop social relationships and is often accompanied by extreme behavioral challenges. Autism spectrum disorders are diagnosed in one in 166 children in the United States, affecting four times as many boys as girls., .