Rare heterozygous truncating variations and risk of autism spectrum disorder: Whole‐exome sequencing of a multiplex family and follow‐up study in a Japanese population. Issue 8 (17th February 2015)

• Record Type: Journal Article
• Authors: Inoue, Emiko; Watanabe, Yuichiro; Egawa, Jun; Sugimoto, Atsunori; Nunokawa, Ayako; Shibuya, Masako; Igeta, Hirofumi; Someya, Toshiyuki
• Is Part Of: Psychiatry and clinical neurosciences. Volume 69:Issue 8(2015:Aug.)
• Page Start: 472
• Page End: 476
• Publication Date: 2015-02-17
• Subjects: Psychiatry -- Periodicals; Neurology -- Periodicals; 616.89
• DOI: 10.1111/pcn.12274
• Languages: English
• ISSNs: 1323-1316

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="pcn12274-sec-0001" sec-type="section"> <title>Aims</title> <p>Rare heterozygous truncating variations in multiplex families with autism spectrum disorder (ASD) are suggested to play a major role in the genetic etiology of ASD. To further investigate the role of rare heterozygous truncating variations, we performed whole‐exome sequencing (WES) in a multiplex ASD family with four affected individuals (two siblings and two maternal cousins), and a follow‐up case–control study in a Japanese population.</p> </sec> <sec id="pcn12274-sec-0002" sec-type="section"> <title>Methods</title> <p>WES was performed in four individuals (a proband, his affected and unaffected siblings, and their putative carrier mother) from the multiplex ASD family. Rare heterozygous truncating variations prioritized in WES were genotyped in 243 patients and 667 controls.</p> </sec> <sec id="pcn12274-sec-0003" sec-type="section"> <title>Results</title> <p>By WES of the multiplex family, we prioritized two rare heterozygous truncating variations, <italic>RPS24</italic> Q191X and <italic>CD300LF</italic> P261fsX266. However, we did not identify these variations in patients or controls in the follow‐up study.</p> </sec> <sec id="pcn12274-sec-0004" sec-type="section"> <title>Conclusions</title> <p>Our findings suggest that two rare heterozygous truncating variations (<italic>RPS24</italic> Q191X and <italic>CD300LF</italic> P261fsX266) are risk candidates for ASD.</p> </sec> </abstract>