Medical Genetics Institute of Henan Province, Henan Provincial Key Laboratory of Genetic Diseases and Functional Genomics, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China.
Medical Genetics Institute of Henan Province, Henan Provincial Key Laboratory of Genetic Diseases and Functional Genomics, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China.
Gene. 2019 Jun 5;700:65-69. doi: 10.1016/j.gene.2019.03.023. Epub 2019 Mar 19.
Adams-Oliver syndrome (AOS) is a rare developmental disorder characterized by the combination of aplasia cutis congenita of the scalp vertex and terminal transverse limb defects. DOCK6 (Dedicator of cytokinesis 6) is one of the six identified AOS genes.
We performed targeted next-generation sequencing (NGS) of a child with an AOS phenotype. Sanger DNA sequencing further validated her lineal consanguinity. To explore the pathological features of the mutation, a minigene assay was used to investigate the effects of the mutation on splicing.
Two compound heterozygous DOCK6 mutations (c.4106+2T>C and c.3063 C>G (p.Y1021*)) were identified in this family, and both mutations have not been reported previously. Sanger DNA sequencing indicated that the mutations were inherited maternally and paternally, respectively. The results of the minigene assay showed that the c.4106+2T>C mutation resulted in aberrant splicing and caused a four-nucleotide insertion in the transcript and a premature stop codon.
Our findings expanded the number of reported cases of this rare disease and the mutation spectrum of DOCK6 mutations, which can serve as the basis for prenatal diagnosis and genetic counseling.
Adams-Oliver 综合征（AOS）是一种罕见的发育障碍，其特征是头皮顶点先天性头皮缺失和末端横断肢体缺陷的组合。DOCK6（胞质分裂蛋白 6）是已鉴定出的 AOS 基因之一。
我们对具有 AOS 表型的儿童进行了靶向下一代测序（NGS）。Sanger DNA 测序进一步验证了她的直系亲属有血缘关系。为了探讨突变的病理特征，我们使用小基因试验来研究突变对剪接的影响。
在这个家庭中发现了两个复合杂合 DOCK6 突变（c.4106+2T>C 和 c.3063 C>G（p.Y1021*）），这两个突变以前都没有报道过。Sanger DNA 测序表明，突变分别从母亲和父亲遗传而来。小基因试验的结果表明，c.4106+2T>C 突变导致异常剪接，并导致转录本中的四个核苷酸插入和提前终止密码子。
我们的发现扩展了这种罕见疾病的报告病例数量和 DOCK6 突变的突变谱，这可以作为产前诊断和遗传咨询的基础。
