当前位置: X-MOL 学术J. Mol. Neurosci. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Functional Analysis of a Compound Heterozygous Mutation in the VPS13B Gene in a Chinese Pedigree with Cohen Syndrome
Journal of Molecular Neuroscience ( IF 2.8 ) Pub Date : 2020-10-06 , DOI: 10.1007/s12031-020-01713-6
Guiyu Lou 1, 2, 3 , Yang Ke 1, 2, 3 , Yuwei Zhang 1, 2, 3 , Guo Liangjie 1, 2, 3 , Samaa Abdelmonem Shama 4 , Na Qi 1, 2, 3 , Litao Qin 1, 2, 3 , Shixiu Liao 1, 2, 3 , Yuanyin Zhao 5
Affiliation  

Cohen syndrome (CS) is an autosomal recessive congenital disorder characterized by mutation in the vacuolar protein sorting 13 homolog B (VPS13B; formerly COH1) gene. In the current study, a Chinese family has two young sibling cases having a developmental delay, physical obesity, high myopia, and a special face, which suspected to be CS. The purpose of the study was to identify variants and further analyze their pathogenicity for CS. Next-generation sequencing (NGS) revealed a compound heterozygous mutation in VPS13B gene in the proband, which comprises a frameshift mutation in NM_017890.4: c.10076_10077delCA (p.T3359fs*29) and a putative splice site mutation in c.6940 + 1G > T. Both Minigene assay in vitro and splicing assay in vivo confirmed that the splicing mutation in c.6940 + 1G > T generates a frameshift transcript with whole exon 38 skipping. Eventually, quantitative real-time PCR demonstrated that either of the two mutations can lead to degradation of the VPS13B gene at the transcriptional level. Functional studies of variants identified in CS patients are essential for their subsequent genetic counseling and prenatal diagnoses and could also be the start point for new therapeutic approaches, currently based only on symptomatic treatment.

更新日期:2020-10-07
down
wechat
bug