Resequencing and Association Analysis of CLN8 with Autism Spectrum Disorder in a Japanese Population

PLoS One. 2015 Dec 14;10(12):e0144624. doi: 10.1371/journal.pone.0144624. eCollection 2015.

Abstract

Rare variations contribute substantially to autism spectrum disorder (ASD) liability. We recently performed whole-exome sequencing in two families with affected siblings and then carried out a follow-up study and identified ceroid-lipofuscinosis neuronal 8 (epilepsy, progressive with mental retardation) (CLN8) as a potential genetic risk factor for ASD. To further investigate the role of CLN8 in the genetic etiology of ASD, we performed resequencing and association analysis of CLN8 with ASD in a Japanese population. Resequencing the CLN8 coding region in 256 ASD patients identified five rare missense variations: g.1719291G>A (R24H), rs201670636 (F39L), rs116605307 (R97H), rs143701028 (T108M) and rs138581191 (N152S). These variations were genotyped in 568 patients (including the resequenced 256 patients) and 1017 controls. However, no significant association between these variations and ASD was identified. This study does not support a contribution of rare missense CLN8 variations to ASD susceptibility in the Japanese population.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Asian People / genetics
  • Autism Spectrum Disorder / genetics*
  • Child
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Japan
  • Male
  • Membrane Proteins / genetics*
  • Middle Aged
  • Mutation, Missense*
  • Pedigree
  • Young Adult

Substances

  • CLN8 protein, human
  • Membrane Proteins

Grants and funding

This work was supported by a grant from the Niigata Medical Association, by a grant from the Japan Foundation for Neuroscience, and by a “Integrated Research on Neuropsychiatric Disorders” of the Strategic Research Program for Brain Sciences from the Japan Agency for Medical Research and development, AMED. The funders had no role in the study design, data collection or analysis, decision to publish, or preparation of the manuscript.