Using Whole-Exome Sequencing to Identify Inherited Causes of Autism

Timothy W. Yu, Maria H. Chahrour, Michael E. Coulter, Sarn Jiralerspong, Kazuko Okamura-Ikeda, Bulent Ataman, Klaus Schmitz-Abe, David A. Harmin, Mazhar Adli, Athar N. Malik, Alissa M. D'Gama, Elaine T. Lim, Stephan J. Sanders, Ganesh H. Mochida, Jennifer N. Partlow, Christine M. Sunu, Jillian M. Felie, Jacqueline Rodriguez, Ramzi H. Nasir, Janice WareRobert M. Joseph, R. Sean Hill, Benjamin Y. Kwan, Muna Al-Saffar, Nahit M. Mukaddes, Asif Hashmi, Soher Balkhy, Generoso G. Gascon, Fuki M. Hisama, Elaine LeClair, Annapurna Poduri, Ozgur Oner, Samira Al-Saad, Sadika A. Al-Awadi, Laila Bastaki, Tawfeg Ben-Omran, Ahmad S. Teebi, Lihadh Ibrahim Al Gazali, Valsamma Eapen, Christine R. Stevens, Leonard Rappaport, Stacey B. Gabriel, Kyriacos Markianos, Matthew W. State, Michael E. Greenberg, Hisaaki Taniguchi, Nancy E. Braverman, Eric M. Morrow, Christopher A. Walsh

Research output: Contribution to journalArticlepeer-review

349 Citations (Scopus)


Despite significant heritability of autism spectrum disorders (ASDs), their extreme genetic heterogeneity has proven challenging for gene discovery. Studies of primarily simplex families have implicated de novo copy number changes and point mutations, but are not optimally designed to identify inherited risk alleles. We apply whole-exome sequencing (WES) to ASD families enriched for inherited causes due to consanguinity and find familial ASD associated with biallelic mutations in disease genes (AMT, PEX7, SYNE1, VPS13B, PAH, and POMGNT1). At least some of these genes show biallelic mutations in nonconsanguineous families as well. These mutations are often only partially disabling or present atypically, with patients lacking diagnostic features of the Mendelian disorders with which these genes are classically associated. Our study shows the utility of WES for identifying specific genetic conditions not clinically suspected and the importance of partial loss of gene function in ASDs.

Original languageEnglish
Pages (from-to)259-273
Number of pages15
Issue number2
Publication statusPublished - Jan 23 2013

ASJC Scopus subject areas

  • General Neuroscience


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