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Study: Half of all autism cases trace to rare gene-disabling mutations

Researchers identify short list of high-impact genetic causes of autism; see potential to guide personalized treatments
September 25, 2015


New research suggests that, in at least half of cases, autism traces to one of roughly 200 gene-disabling mutations found in the child but neither parent.

Many of these “high-impact” mutations, the investigators found, completely disable genes crucial to early brain development. In addition, they appear to be more common among people who are severely disabled by autism versus those only mildly affected.

The study, by scientists at Cold Spring Harbor Laboratory, New York, appears this week in the Proceedings of the National Academy of Sciences. (Download the full paper here.)

The DNA analysis of 1,866 families affected by autism looked at the growing list of more than 500 gene changes known to increase autism risk. It identified 239 genes with the greatest likelihood of causing autism if any one of them was disabled by a mutation.

The study’s findings also run counter to the commonly held idea that autism almost always results from a complex interplay of common and subtle gene changes and environmental influences – none of which would cause autism by itself.

This shortened “priority list” may prove particularly helpful to doctors and geneticists using genetic screens to guide diagnosis and personalized treatment, comments Mathew Pletcher, head of Autism Speaks' genomic discovery program. Dr. Pletcher was not involved in the research.

“These findings argue strongly that genetics can provide meaningful answers for a significant portion of individuals with autism,” Dr. Pletcher explains. “From this extends the idea we can provide better care and support by deepening our understanding of the health risks that arise from each person’s specific genetic disruption.” 

Autism Speaks’ MSSNG program aims to drive such advances by providing the global autism research community with an unprecedented collection of 10,000 whole genome sequences from people affected by autism and their families. These genomes – and the sophisticated tools to work with them – are being hosted on the Google Cloud platform. (See video below.)

MSSNG: Changing the future of autism through open science. Learn more here.

Mutation in child but neither parent
Most of the high-impact mutations identified in the new study occurred in the child but neither parent. Such newly arising, or de novo, mutations first occur in the mother’s egg, the father’s sperm or early in embryo development.

Some of the first research out of the Autism Speaks MSSNG project implicated de novo mutations in the higher rates of autism seen among children of older parents. With age, a woman’s eggs and a man’s sperm-producing cells tend to accumulate these mutations. And one potential source of these accumulating mutations, Dr. Pletcher notes, is lifetime exposure to environmental “insults” such as radiation and toxic chemicals (naturally occurring or otherwise).

To learn more about the interaction of environment influences and genetics in autism, Dr. Pletcher invites readers to participate in a free October 1st webinar. Learn more here.