复发性新生突变揭示了单纯型自闭症风险背后的新基因。

Recurrent de novo mutations implicate novel genes underlying simplex autism risk.

作者信息

O'Roak B J, Stessman H A, Boyle E A, Witherspoon K T, Martin B, Lee C, Vives L, Baker C, Hiatt J B, Nickerson D A, Bernier R, Shendure J, Eichler E E

机构信息

Department of Genome Sciences, University of Washington School of Medicine, Seattle, Washington 98195, USA.

Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, Washington 98195, USA.

出版信息

Nat Commun. 2014 Nov 24;5:5595. doi: 10.1038/ncomms6595.

DOI:10.1038/ncomms6595

PMID:25418537

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4249945/

Abstract

Autism spectrum disorder (ASD) has a strong but complex genetic component. Here we report on the resequencing of 64 candidate neurodevelopmental disorder risk genes in 5,979 individuals: 3,486 probands and 2,493 unaffected siblings. We find a strong burden of de novo point mutations for these genes and specifically implicate nine genes. These include CHD2 and SYNGAP1, genes previously reported in related disorders, and novel genes TRIP12 and PAX5. We also show that mutation carriers generally have lower IQs and enrichment for seizures. These data begin to distinguish genetically distinct subtypes of autism important for aetiological classification and future therapeutics.

摘要

自闭症谱系障碍（ASD）具有强大但复杂的遗传成分。在此，我们报告了对5979名个体中64个候选神经发育障碍风险基因的重测序结果：3486名先证者和2493名未受影响的同胞。我们发现这些基因存在大量新生点突变，并特别涉及9个基因。其中包括CHD2和SYNGAP1，这两个基因先前在相关疾病中已有报道，还有新基因TRIP12和PAX5。我们还表明，突变携带者的智商通常较低，且癫痫发作更为常见。这些数据开始区分出对病因分类和未来治疗具有重要意义的自闭症遗传不同亚型。