Newswise — Mutations in three new genes have been linked to autism, according to new studies including one with investigators at Mount Sinai School of Medicine. All three studies include lead investigators of the Autism Sequencing Consortium (ASC). The findings, in a trio of papers revealing new genetic targets in autism, are published in the April 4th online issue of the journal Nature. The studies provide new insights into important genetic changes and the many biological pathways that lead to autism spectrum disorders (ASD).

Gene mutations are glitches in DNA which can put you at risk for a particular disease. The genes with mutations identified in the studies – CHD8, SNC2A, and KATNAL2 – were discovered with a new state-of-the-art genomics technology known as exome sequencing, where all protein coding regions of the genome, called the exome, are analyzed. The researchers say that with further characterization of the genes and sequencing of genes in thousands of families, they will be able to develop novel therapeutics and preventive strategies for autism.

“We now have a good sense of the large number of genes involved in autism and have discovered about 10 percent of them,” said Joseph Buxbaum, PhD, Director of the Seaver Autism Center and Professor of Psychiatry, Genetics and Genomic Sciences, and Neuroscience at Mount Sinai School of Medicine. “We need to study many more parents and their affected children if we are to uncover the genes important in ASD. As these genes are further characterized, this will lead to earlier diagnosis and novel drug development. This work is crucial for advancing autism treatment.”

In the study, ASC researchers hypothesized that de novo mutations account for a substantial fraction of the risk for autism. De novo gene mutations are mutations that show up in affected children for the first time and result from mutations in the production of sperm or egg.

Founded by Dr. Buxbaum, the Autism Sequencing Consortium is an international group of autism genetics researchers that is working to identify additional genetic causes of autism through large-scale next-generation sequencing. The institutions involved in this study sequenced data from more than 500 families (both parents and the affected child), examining the protein-enriched areas of the genome.

“When the same mutations are found in multiple affected children and none are found in children without autism, we believe that we have identified mutations that collectively affect a higher proportion of individuals with autism,” said Dr. Buxbaum. “Our studies revealed that the proteins encoded by the mutated genes interact with each other far more than expected, demonstrating significantly greater connectivity than would be expected.”

Two other papers from groups participating in the Autism Sequencing Consortium are also featured in the same issue of Nature. Led by Matthew State, PhD, Yale School of Medicine, the first identified several highly disruptive mutations in genes associated with ASD. The results show that multiple variants on one gene identify risk factors for ASD. The second study led by Evan Eichler, PhD at the University of Washington discovered that certain mutations associated with ASD are mainly of paternal origin. Their findings also support previous research showing an increased risk of developing ASD in children of older fathers.

This research conducted at Mount Sinai was supported by grants from the National Institutes of Health and the Seaver Foundation. Dr. Buxbaum coauthored the paper with several Mount Sinai investigators, including Avi Ma’ayan, PhD, Assistant Professor of Pharmacology and Systems Therapeutics; Vladamir Makarov, Computer Scientist, Psychiatry; Guiqing Cai, MD, PhD, Instructor, Psychiatry; Omar J. Jabado, PhD, Instructor, Genetics and Genomic Sciences; Seungtai Yoon, PhD, Assistant Professor of Psychiatry, and Jayon Lihm, PhD student.

Mount Sinai also collaborated on this study with researchers from Massachusetts General Hospital and Harvard Medical School; the Broad Institute of Harvard and MIT; Carnegie Mellon University; Baylor College of Medicine; University of Pennsylvania; Vanderbilt University; Johns Hopkins University; Hudson Alpha Institute for Biotechnology in Huntsville, Alabama; Université Pierre et Marie Curie in France; University of Texas Health Science Center; University of Illinois at Chicago; and University of Pittsburgh.

Co-directed by Drs. Buxbaum and State, the ASC shares all parallel sequencing data in autism samples. Through the efforts of the Seaver Autism Center at Mount Sinai School of Medicine and 19 other institutions across the United States, Canada, Europe, and Asia, the autism genetics community is making great strides toward understanding the genetic changes and biological pathways important in autism susceptibility.

About the Seaver Autism CenterThe Seaver Autism Center recently launched the 10,000 Autism Genomes Project, to discover and characterize all the main genes involved in autism. The Seaver Center is the lead site for the initiative. The Center also conducts progressive research studies aimed at understanding the multiple causes of autism spectrum disorders and strives to develop innovative diagnostics and treatments into the provision of personalized, comprehensive assessment and care for people with ASDs. It includes a multidisciplinary team of experts that uses genetics, molecular biology, model systems, neuroimaging, and experimental therapeutics to work with patients and families. For more information, visit

About The Mount Sinai Medical CenterThe Mount Sinai Medical Center encompasses both The Mount Sinai Hospital and Mount Sinai School of Medicine. Established in 1968, Mount Sinai School of Medicine is one of the leading medical schools in the United States. The Medical School is noted for innovation in education, biomedical research, clinical care delivery, and local and global community service. It has more than 3,400 faculty in 32 departments and 14 research institutes, and ranks among the top 20 medical schools both in National Institutes of Health (NIH) funding and by US News and World Report.

The Mount Sinai Hospital, founded in 1852, is a 1,171-bed tertiary- and quaternary-care teaching facility and one of the nation’s oldest, largest and most-respected voluntary hospitals. In 2011, US News and World Report ranked The Mount Sinai Hospital 16th on its elite Honor Roll of the nation’s top hospitals based on reputation, safety, and other patient-care factors. Of the top 20 hospitals in the United States, Mount Sinai is one of 12 integrated academic medical centers whose medical school ranks among the top 20 in NIH funding and US News and World Report and whose hospital is on the US News and World Report Honor Roll. Nearly 60,000 people were treated at Mount Sinai as inpatients last year, and approximately 560,000 outpatient visits took place. For more information, visit

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