Whole-exome sequencing identifies two novel missense mutations (p.L111P and p.R3048C) of RYR3 in a Vietnamese patient with autism spectrum disorders
Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders characterized by ritualistic-repetitive behaviors and impaired verbal and non-verbal communication. Boys are more likely to be diagnosed with ASD than girls. Genetics have been shown to play a key role in the etiology of autism. Many genes were found to be implicated in the inheritance of idiopathic autism. Analysis of mutation abnormalities associated with autism contributes significantly to the identification of autism candidate genes. Whole-exome sequencing has been shown as an application of the next generation sequencing technology used to determine the variations of all coding regions, or exons of the known genes. In the present study, we have found two novel heterozygous missense mutations (p.L111P and p.R3048C) on the RYR3 gene, which was located in the autism susceptibility region (15q14-q15) in a 9-year-old boy with ASD. Therefore, the sequence missense mutations provide the first suggestive link between a genetic abnormality in the RYR3 gene and a neurodevelopmental disorder.
KeywordsAutistic spectrum disorder Autism Ca2+ channel RYR3 gene Whole-exome sequencing
- Ashley-Koch AE, Mei H, Jaworski J, Ma DQ, Ritchie MD, Menold MM, Delong GR, Abramson RK, Wright HH, Hussman JP et al (2006) An analysis paradigm for investigating multi-locus effects in complex disease: examination of three GABA receptor subunit genes on 15q11-q13 as risk factors for autistic disorder. Ann Hum Genet 70:281–292CrossRefPubMedGoogle Scholar
- Association AP (2000) Diagnostic and statistical manual of mental disorders: DSM-IV-TR, 4th edn. American Psychiatric Association, Washington, DCGoogle Scholar
- Chahrour MH, Yu TW, Lim ET, Ataman B, Coulter ME, Hill RS, Stevens CR, Schubert CR, Collaboration AAS, Greenberg ME et al (2012) Whole-exome sequencing and homozygosity analysis implicate depolarization-regulated neuronal genes in autism. PLoS Genet 8:e1002635CrossRefPubMedPubMedCentralGoogle Scholar
- Matsuo N, Tanda K, Nakanishi K, Yamasaki N, Toyama K, Takao K, Takeshima H, Miyakawa T (2009) Comprehensive behavioral phenotyping of ryanodine receptor type 3 (RyR3) knockout mice: decreased social contact duration in two social interaction tests. Front Behav Neurosci 3:3PubMedPubMedCentralGoogle Scholar