Recent studies of autism spectrum disorder (ASD) and childhood apraxia of speech (CAS) have resulted in conflicting conclusions regarding the comorbidity of these disorders on phenotypic grounds. In a nuclear family with two dually affected and one unaffected offspring, whole-exome sequences were evaluated for single nucleotide and indel variants and CNVs. The affected siblings but not the unaffected sibling share a rare deleterious compound heterozygous mutation in WWOX, implicated both in ASD and motor control. In addition, one of the affected children carries a rare deleterious de novo mutation in the ASD candidate gene RIMS1. The two affected children but not their unaffected sibling inherited deleterious variants with relevance for ASD and/or CAS. WWOX, RIMS1, and several of the genes harboring the inherited variants are expressed in the brain during prenatal and early postnatal development. Results suggest compound heterozygosity as a cause of ASD and CAS, pleiotropic gene effects, and potentially additional, complex genetic effects.

中文翻译：

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患有自闭症谱系障碍和严重言语障碍的两个兄弟姐妹的外显子测序表明多效和复杂效应。

自闭症谱系障碍（ASD）和儿童言语失用症（CAS）的最新研究已得出关于这些疾病以表型为基础的合并症的矛盾结论。在有两个受到双重影响和一个未受影响的后代的核心家庭中，评估了全外显子序列的单核苷酸和插入缺失变异体和CNV。受影响的同胞而不是未受影响的同胞在WWOX中共有罕见的有害复合杂合突变，与ASD和运动控制有关。此外，其中一名受影响的儿童在ASD候选基因RIMS1中携带罕见的有害的从头突变。这两个受影响的孩子，而不是他们未受影响的兄弟姐妹，继承了与ASD和/或CAS有关的有害变种。WWOX，RIMS1，在出生前和出生后早期，在大脑中表达了一些带有遗传变异的基因。结果表明，复合杂合性是导致ASD和CAS的原因，多效性基因效应以及潜在的其他复杂遗传效应。