title: 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.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Psychiatry, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.
authors.forename: Emiko
authors.initials: E
authors.lastname: Inoue
authors.affiliation: Department of Psychiatry, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.|Division of Medical Education, Comprehensive Medical Education Center, School of Medicine, Faculty of Medicine, Niigata University, Niigata, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Watanabe
authors.affiliation: Department of Psychiatry, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.|Department of Pediatric Psychiatry, Center for Transdisciplinary Research, Niigata University, Niigata, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Egawa
authors.affiliation: Department of Psychiatry, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.
authors.forename: Atsunori
authors.initials: A
authors.lastname: Sugimoto
authors.affiliation: Department of Psychiatry, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.|Oojima Hospital, Niigata, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Nunokawa
authors.affiliation: Department of Psychiatry, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.|Health Administration Center, Headquarters for Health Administration, Niigata University, Niigata, Japan.
authors.forename: Masako
authors.initials: M
authors.lastname: Shibuya
authors.affiliation: Department of Psychiatry, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Igeta
authors.affiliation: Department of Psychiatry, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Someya
mesh_terms: D044466:Asian People / Q000235:genetics* / Q000523:psychology; D000067877:Autism Spectrum Disorder / Q000235:genetics*; D016022:Case-Control Studies; D059472:Exome / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D007564:Japan; D008297:Male; D011971:Receptors, Immunologic / Q000235:genetics*; D012269:Ribosomal Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: C519443:CD300LF protein, human; C489053:RPS24 protein, human; D011971:Receptors, Immunologic; D012269:Ribosomal Proteins
keywords: Japanese; autism spectrum disorder; multiplex family; truncating variation; whole-exome sequencing