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A novel pathogenic deletion in ISPD causes Walker-Warburg syndrome in a Chinese family

文献类型：期刊论文

作者Shi, Yuting5,6; Fu, Yimei2,3,4; Tao, Zhouteng1; Yong, Wenjing2,3,4; Peng, Huirong5,6; Jian, Wenyang2,3,4; Chen, Gang2,3,4; Guo, Manhui2,3,4; Zhao, Yanhua2,3,4; Yao, Ruojin2,3,4
刊名GENES & GENOMICS
出版日期2022-08-11
页码7
关键词ISPD Congenital hydrocephalus Walker-Warburg syndrome Exome sequencing Mutation
ISSN号1976-9571
DOI10.1007/s13258-022-01296-z
通讯作者Guo, Dewei(guodewei@csu.edu.cn)
英文摘要Background Walker-Warburg syndrome (WWS) is a genetically heterogeneous disease that often presents with complex brain and eye malformations and congenital muscular dystrophy. Mutations of the ISPD gene have been identified as one of the most frequent causes of WWS. Objective The current study aimed to identify the cause of severe congenital hydrocephalus and brain dysplasia in our subject. Methods 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. Results 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. Conclusion 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.
WOS关键词DEFECTIVE GLYCOSYLATION ; MUSCULAR-DYSTROPHIES ; DYSTROGLYCAN ; MUTATIONS ; BRAIN
资助项目National Nature Science Foundation of China[81600995] ; Nature Science Foundation of Hunan Province[2021JJ40984] ; Scientific Research Project of Hunan Provincial Health Commission[C2019191] ; International Scientific Exchange Foundation of China (ISEFC)[Z2019LHNN001] ; International Scientific Exchange Foundation of China (ISEFC)[Z2019LHNN002] ; Hunan Science and Technology Innovation Plan[2020SK53712] ; Xiangya Hospital Clinical Research Project[2018101046]
WOS研究方向Biochemistry & Molecular Biology ; Biotechnology & Applied Microbiology ; Genetics & Heredity
语种英语
WOS记录号WOS:000839493400002
出版者SPRINGER
源URL[http://119.78.100.183/handle/2S10ELR8/302287]  
专题新药研究国家重点实验室
通讯作者Guo, Dewei
作者单位1.Chinese Acad Sci, Ctr Drug Safety Evaluat & Res, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, Peoples R China
2.Cent South Univ, Fetal Med Ctr, Changsha, Peoples R China
3.Cent South Univ, Xiangya Hosp, Dept Obstet Fetal Med, Changsha, Hunan, Peoples R China
4.Cent South Univ, Xiangya Hosp, Dept Obstet, Changsha, Peoples R China
5.Cent South Univ, Key Lab Hunan Prov Neurodegenerat Disorders, Changsha, Peoples R China
6.Cent South Univ, Xiangya Hosp, Dept Neurol, Changsha, Peoples R China
推荐引用方式
GB/T 7714		 Shi, Yuting,Fu, Yimei,Tao, Zhouteng,et al. A novel pathogenic deletion in ISPD causes Walker-Warburg syndrome in a Chinese family[J]. GENES & GENOMICS,2022:7.
APA Shi, Yuting.,Fu, Yimei.,Tao, Zhouteng.,Yong, Wenjing.,Peng, Huirong.,...&Guo, Dewei.(2022).A novel pathogenic deletion in ISPD causes Walker-Warburg syndrome in a Chinese family.GENES & GENOMICS,7.
MLA Shi, Yuting,et al."A novel pathogenic deletion in ISPD causes Walker-Warburg syndrome in a Chinese family".GENES & GENOMICS (2022):7.

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来源：上海药物研究所

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