The current study aimed to identify the cause of severe congenital hydrocephalus and brain dysplasia in our subject.
Genomic DNA was extracted from the fetus\'s umbilical cord blood and peripheral venous blood of the parents. The genetic analysis included whole-exome sequencing and qPCR. Additionally, in silico analysis and cellular experiments were performed.
We identified a novel homozygous deletion of exons 7 to 9 in the ISPD gene of the fetus with WWS. In silico analysis revealed a defective domain structure in the C-terminus domain of the ISPD. Analysis of the electrostatic potential energy showed the formation of a new binding pocket formation on the surface of the mutant ISPD gene (ISPD-del ex7-9). Cellular study of the mutant ISPD revealed a significant change in its cellular localization, with the ISPD-del ex7-9 protein translocating from the cytoplasm to the nucleus compared to wild-type ISPD, which is mostly present in the cytoplasm.
The present study expands the mutational spectrum of WWS caused by ISPD mutations. Importantly, our work suggests that whole-exome sequencing could be considered as a diagnostic option for fetuses with congenital hydrocephalus and brain malformations when karyotype or chromosomal microarray analysis fails to provide a definitive diagnosis.
目的:当前的研究旨在确定我们受试者中严重的先天性脑积水和脑发育不良的原因。
方法:从胎儿的脐带血和父母的外周静脉血中提取基因组DNA。
结果:我们在WWS胎儿的ISPD基因中鉴定出外显子7至9的新纯合缺失。
结论:本研究扩展了ISPD突变引起的WWS突变谱。