Mutations in a father’s sperm could predict the risk of autism in children: Study

Mutations were present in up to 15% of the sperm cells in fathers, information that could not be determined through other means, such as blood samples, say experts


                            Mutations in a father’s sperm could predict the risk of autism in children: Study
Researchers analyzed the sperm of eight fathers who were already parents of children with an autism spectrum disorder. They found measuring mutations in sperm might reveal risk for autism in future children. (Getty Images)

Disease-causing changes or mutations found only in the sperm of the father could predict the risk of autism in children.

A team of scientists, led by researchers from the University of California (UC) San Diego School of Medicine tested the sperm of fathers who were already parents of children with an autism spectrum disorder (ASD). They found that the disease-causing mutations were present in up to 15% of the fathers’ sperm cells -- information that could not be determined through other means such as blood samples.

The causes of autism spectrum disorder (ASD) in children are not fully understood, and researchers believe that both genetics and the environment have a role to play. In some cases, the disorder is linked to mutations that appear only in the child and are not inherited from either parent’s DNA.

Clinicians continue to face an ever-increasing incidence of autism spectrum disorders, without effective strategies available to prevent disease or counsel families.

Recent studies suggest gene-damaging spontaneous mutations are involved in at least 10% to 30% of ASD cases. Researchers believe that the number of mutations increases with the father’s age at time of conception. Such mutations occur spontaneously in parents’ sperm or eggs or during fertilization. When a disease-causing mutation occurs for the first time in a family, the probability that it could happen again in a future child is not known. Thus, families must make a decision with a great deal of uncertainty, say experts.

According to the researchers, they have developed a method to measure disease-causing mutations found only in the sperm of the father and assess chances the mutations will cause disease. The team says the new method -- described in Nature Medicine -- provide expectant parents with a more accurate assessment of autism risk in future children.

“Autism afflicts 1 in 59 children and we know that a significant portion is caused by de novo (spontaneous) DNA mutations, yet we are still blind to when and where these mutations will occur,” says Dr. Jonathan Sebat, professor and chief of the Beyster Center for Molecular Genomics of Neuropsychiatric Diseases at UC San Diego School of Medicine, in the analysis.

“With our new study, we can trace some of these mutations back to the father, and we can directly assess the risk of these same mutations occurring again in future children,” says Dr. Sebat, a co-senior author of the study.

In this illustration, mutated sperm are depicted in red. Researchers have developed a way to quantify those mutations and assess chances the mutations will cause disease. (UC San Diego Health Sciences)

The US Centers for Disease Control and Prevention (CDC) describes autism spectrum disorder as a developmental disability that can cause significant social, communication and behavioral challenges. For 2014, the overall prevalence of ASD in the US was estimated at 16.8 per 1,000 (one in 59) children aged 8 years.

“There are likely many causes for multiple types of ASD. There may be many different factors that make a child more likely to have an ASD, including environmental, biologic and genetic factors. Most scientists agree that genes are one of the risk factors that can make a person more likely to develop this disorder,” says CDC.

For their study, the researchers analyzed the sperm of eight fathers of autistic children. The objective, says the team, was to look for the presence of multiple, genetically different sets of cells in the same person, a condition called mosaicism.

“While medical textbooks teach us that every cell in the body has an identical copy of DNA, this is fundamentally not correct. Mutations occur every time a cell divides, so no two cells in the body are genetically identical,” says first author Dr. Martin Breuss, an assistant project scientist in the lab of Dr. Joseph Gleeson, also a co-senior study author.

The researchers explain that mosaicism can cause cancer or can be silent in the body. If a mutation occurs early in development, then it will be shared by many cells within the body. “But if a mutation happens just in sperm, then it can show up in a future child, but not cause any disease in the father,” says Breuss.

The researchers used a technique called deep whole-genome sequencing. They found genetic variants in the children that were matched only in the fathers’ sperm.

Previously research by the team, says Dr. Gleeson, showed that mosaicism in a child can lead to diseases like epilepsy. “Here, we show that mosaicism in one of the parents is at least as important when thinking about genetic counseling,” says Dr. Gleeson, professor of neuroscience at UC San Diego School of Medicine and director of neuroscience research at the Rady Children’s Institute for Genomic Medicine.

The researchers said that if the study is developed into a clinical test, fathers could have their sperm studied to determine their precise risk of recurrence in future children. The method might also be applied to men who have not had children yet, but who want to know the risk of having a child with a disease, says the team.

Disclaimer : This article is for informational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition.