健康与遗传心理学研究室知识库

Autism spectrum disorders (ASDs) are common neurodevelopmental disorders with a strong genetic etiology. However, due to the extreme genetic heterogeneity of ASDs, traditional approaches for gene discovery are challenging. Next-generation sequencing technologies offer an opportunity to accelerate the identification of the genetic causes of ASDs. Here, we report the results of whole-exome sequence in a cohort of 20 ASD patients. By extensive bioinformatic analysis, we identified novel mutations in seven genes that are implicated in synaptic function and neurodevelopment. After sequencing an additional 47 ASD samples, we identified three different missense mutations in ANK3 in four unrelated ASD patients, one of which, c.4705T>G (p.S1569A), is a de novo mutation. Given the fact that ANK3 has been shown to strongly associate with schizophrenia and bipolar disorder, our findings support an association between ANK3 mutations and ASD susceptibility and imply a shared molecular pathophysiology between ASDs and other neuropsychiatric disorders. Hum Mutat 33:16351638, 2012. (c) 2012 Wiley Periodicals, Inc.

Contract grant sponsors: Major State Basic Research Development Program of China (2012CB517902 and 2012CB517904); International S&T Cooperation Program of China (2011DFA30670); Natural Science Foundation of Zhejiang Province (Z2110521); Autism Speaks (to YHJ).We appreciate Yooji Lee and Xinyu Cao for technical support. We also thank Jennifer Goldstein for critical reading of the manuscript. We gratefully acknowledge the resources provided by the Autism Genetic Resource Exchange (AGRE) Consortium* and the participating AGRE families. The Autism Genetic Resource Exchange is a program of Autism Speaks and is supported, in part, by grant 1U24MH081810 from the National Institute of Mental Health to Clara M. Lajonchere (PI).