Functional Analysis of a Compound Heterozygous Mutation in the VPS13B Gene in a Chinese Pedigree with Cohen Syndrome
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Functional Analysis of a Compound Heterozygous Mutation in the VPS13B Gene in a Chinese Pedigree with Cohen Syndrome 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 Received: 9 August 2020 / Accepted: 15 September 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract 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. Keywords VPS13B gene . Cohen syndrome . Mutation . Functional analysis . Pedigree
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12031-020-01713-6) contains supplementary material, which is available to authorized users. Highlight A compound heterozygous mutation in VPS13B gene was identified in a Chinese Cohen syndrome family. This splice site variant generates a frameshift transcript with whole exon skipping. Either of the two mutations can lead to degradation of the VPS13B gene at the transcriptional level in vivo. Splice site variant in NM_017890.4: c.6940 + 1G > T detected in three sporadically Chinese CS families could be a recurrent mutation for CS in Chinese population. * Shixiu Liao [email protected]
3
Medical College of Henan University, Zhengzhou 450003, China
* Yuanyin Zhao [email protected]
4
National Organization for Drug Control and Research, Governorate, Giza, Egypt
1
Medical Genetics Institute of Henan Province, Henan Provincial People’s Hospital, Zhengzhou 450003, China
5
2
People’s Hospital of Zhengzhou University, Zhengzhou 450003, China
Department of Biochemistry and Molecular Biology, College of Basic Medical Science, Army Medical University, No. 30 Gaotanyan Street, Chongqing 400038, China
J Mol Neurosci
Introduction Cohen syndrome (CS) was firstly discovered by M. Micha
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