Xiong Jianjun, Xiang Bingwu, Chen Xiang, Cai Tao
College of Basic Medical Science, Jiujiang University, Jiujiang, Jiangxi.
Experimental Medicine Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD.
Medicine (Baltimore). 2019 Mar;98(10):e14780. doi: 10.1097/MD.0000000000014780.
Holoprosencephaly (HPE) is a severe congenital brain malformation resulting from failed or incomplete forebrain division in early pregnancy.
In this study, we reported a 9-month old infant girl with mild microcephaly, semilobor HPE, and arachnoid cyst.
Potential genetic defects were screened directly using trio-case whole exome sequencing (WES) rather than traditional karyotype, microarray, and Sanger sequencing of select genes.
A previous unpublished de novo missense mutation (c.1069C >G, p.H357D) in the 3rd zinc finger domain (ZFD3) of the ZIC2 gene was identified in the affected individual, but not in the parents. Sanger sequencing using specific primers verified the mutation. Extensive bioinformatics analysis confirmed the pathogenicity of this extremely rare mutation. Phenotype-genotype analysis revealed significant correlation between the 3rd zinc-finger domain with semilobor HPE.
These findings expanded the spectrum of the ZIC2 gene mutations and associated clinical manifestations, which is the first identification of a mutated ZIC2 gene in a Han infant girl with mild microcephaly, semilobor HPE, and arachnoid cyst.
前脑无裂畸形（HPE）是一种严重的先天性脑畸形，由妊娠早期前脑分裂失败或不完全所致。
在本研究中，我们报告了一名9个月大的女婴，患有轻度小头畸形、半叶型前脑无裂畸形和蛛网膜囊肿。
直接使用三联体全外显子组测序（WES）筛查潜在的基因缺陷，而非传统的核型分析、微阵列分析和特定基因的桑格测序。
在患病个体中鉴定出ZIC2基因第3个锌指结构域（ZFD3）中一个先前未发表的新生错义突变（c.1069C>G，p.H357D），但父母中未发现。使用特异性引物的桑格测序验证了该突变。广泛的生物信息学分析证实了这种极其罕见突变的致病性。表型-基因型分析显示第3个锌指结构域与半叶型前脑无裂畸形之间存在显著相关性。
这些发现扩展了ZIC2基因突变谱及相关临床表现，这是首次在一名患有轻度小头畸形、半叶型前脑无裂畸形和蛛网膜囊肿的汉族女婴中鉴定出ZIC2基因突变。
