Resequencing and Association Analysis of CLN8 with Autism Spectrum Disorder in a Japanese Population.
Resequencing and Association Analysis of CLN8 with Autism Spectrum Disorder in a Japanese Population.
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DOI：
10.1371/journal.pone.0144624
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Someya T
中科院分区：
文献类型：
--
作者：
Inoue E;Watanabe Y;Xing J;Kushima I;Egawa J;Okuda S;Hoya S;Okada T;Uno Y;Ishizuka K;Sugimoto A;Igeta H;Nunokawa A;Sugiyama T;Ozaki N;Someya T
罕见的变异在很大程度上导致自闭症谱系障碍（ASD）的易感性。我们最近在两个有受影响兄弟姐妹的家庭中进行了全外显子组测序，然后进行了随访研究，并确定了蜡样脂褐质沉积症神经元8（癫痫，进行性伴精神发育迟滞）（CLN8）作为ASD的潜在遗传危险因素。为了进一步研究CLN8在ASD遗传病因学中的作用，我们在日本人群中对CLN8与ASD进行了重新测序和关联分析。对256名ASD患者的CLN 8编码区进行重新测序，发现了五种罕见的错义变异：g.1719291G>A（R24 H）、rs201670636（F39 L）、rs116605307（R97 H）、rs143701028（T108 M）和rs138581191（N152 S）。这些变异在568名患者（包括重新测序的256名患者）和1017名对照中进行了基因分型。然而，这些变化和ASD之间没有显着关联。这项研究不支持罕见的错义CLN8变异对日本人群ASD易感性的贡献。
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.