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Case Reports
. 2021 May;71(5):943-952.
doi: 10.1007/s12031-020-01713-6. Epub 2020 Oct 6.

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  5   6   7 , Yuanyin Zhao  8
Affiliations
Case Reports

Functional Analysis of a Compound Heterozygous Mutation in the VPS13B Gene in a Chinese Pedigree with Cohen Syndrome

Guiyu Lou et al. J Mol Neurosci. 2021 May.

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: Cohen syndrome; Functional analysis; Mutation; Pedigree; VPS13B gene.

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References

    1. Cohen MMJ, Hall BD, Smith DW, Graham CB, Lampert KJ (1973) New syndrome with hypotonia, obesity, mental deficiency and facial, oral, ocular and limb anomalies. J Pediatr 83:280–284 - DOI
    1. Duplomb L, Duvet S, Picot D, Jego G, El Chehadeh-Djebbar S, Marle N, Gigot N, Aral B, Carmignac V, Thevenon J (2014) Cohen syndrome is associated with major glycosylation defects. Hum Mol Genet 23:2391–2399 - DOI
    1. El Chehadeh S, Aral B, Gigot N, Thauvin-Robinet C, Donzel A, Delrue MA, Lacombe D, David A, Burglen L, Philip N et al (2010) Search for the best indicators for the presence of a VPS13B gene mutation and confirmation of diagnostic criteria in a series of 34 patients genotyped for suspected Cohen syndrome. J Med Genet 47:549–553 - DOI
    1. Falk MJ, Feiler HS, Neilson DE, Maxwell K, Lee JV, Segall SK, Robin NH, Wilhelmsen KC, Träskelin AL, Kolehmainen J, Lehesjoki AE, Wiznitzer M, Warman ML (2004) Cohen syndrome in the Ohio Amish. Am J Med Genet A 128A:23–28 - DOI
    1. Hennies HC, Rauch A, Seifert W, Schumi C, Moser E, Al-Taji E, Tariverdian G, Chrzanowska KH, Krajewska-Walasek M, Rajab A et al (2004) Allelic heterogeneity in the COH1 gene explains clinical variability in Cohen syndrome. Am J Hum Genet 75(1):138–145 - DOI

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