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.

AIMS: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. METHODS: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. RESULTS:By WES of the multiplex family, we prioritized two rare heterozygous truncating variations, RPS24 Q191X and CD300LF P261fsX266. However, we did not identify these variations in patients or controls in the follow-up study. CONCLUSIONS:Our findings suggest that two rare heterozygous truncating variations (RPS24 Q191X and CD300LF P261fsX266) are risk candidates for ASD.

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