Whole Exome Sequencing Identifies a Novel Homozygous Duplication Mutation in the VPS13B Gene in an Indian Family with Cohen Syndrome

Kaushik, Pankhuri; Mahajan, Naresh; Girimaji, Satish Chandra; Kumar, Arun

doi:10.1007/s12031-020-01530-x

Cited by 8 publications

(3 citation statements)

References 14 publications

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“…15 Cohen syndrome is characterized by myopia, retinal dystrophy, neutropenia, short stature, microcephaly, persistent hypotonia, developmental retardation, truncated obesity, joint hyperextension, characteristic facial features, and overly friendly behavior. [1][2][3]16 Approximately half of patients with Cohen syndrome exhibit decreased fetal movement during gestation and hypotonia during infancy, which can sometimes lead to breathing and feeding difficulties. 1 Almost all patients have varying degrees of language and motor retardation, and most patients are cheerful and friendly, but some studies have reported that patients may also have a combination of autism spectrum disorders.…”

Section: Discussionmentioning

confidence: 99%

Identification of a Novel VPS13B Mutation in a Chinese Patient with Cohen Syndrome by Whole-Exome Sequencing

Hu¹,

Huang²,

Liu³

et al. 2021

PGPM

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Objective: The present study aims to investigate the clinical features and diagnostic characteristics of children with Cohen syndrome caused by the vacuolar protein sorting 13 homolog B (VPS13B) gene mutation and to review the relevant literature to provide a reference for genetic counseling and the diagnosis of Cohen syndrome. Methods: The clinical data and molecular genetic test results of a child with Cohen syndrome were retrospectively analyzed and a review of the relevant literature was conducted. Results: A two-year-and-four-month-old boy was referred to the hospital for recurrent fever and shortness of breath. On physical examination, the boy was found to have growth retardation, thick bushy hair, microcephaly, hypertelorism, down-slanting palpebral fissures, and hypotonia. Genetic testing was performed, and the results suggested the presence of exon 20-32 heterozygous deletion and c.8275 delC (p.R2759 fs*18) heterozygous variant on the VPS13B gene from phenotypically normal parents. These two mutation loci have not been reported in the literature, and they were predicted by relevant software to be pathogenic variants. Conclusion:We identified two novel variants in the VPS13B gene (exon 20-32 heterozygous deletion and c.8275 delC heterozygous variant) in a boy with Cohen syndrome, thus extending the spectrum of VPS13B gene variants in patients with Cohen syndrome.

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Section: Discussionmentioning

confidence: 99%

Identification of a Novel VPS13B Mutation in a Chinese Patient with Cohen Syndrome by Whole-Exome Sequencing

Hu¹,

Huang²,

Liu³

et al. 2021

PGPM

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“…Posteriorly, an extended panel of 16 Finnish families with Cohen syndrome underwent linkage disequilibrium and haplotype analysis, allowing for a refined mapping of the VPS13B gene [3]. Since then, more than 200 cases have been reported worldwide [4], and whole-exome sequencing has enabled the documentation of multiple VPS13B pathogenic variants [5][6][7][8][9][10]. The VPS13B/COH1 gene encodes the VPS13B protein, which is part of the cell's Golgi apparatus and is involved in protein glycosylation and sorting and transporting proteins inside the cell.…”

Section: Introductionmentioning

confidence: 99%

Cohen Syndrome: Novel VPS13B Genetic Variants in a Male Portuguese Patient with Pigmentary Retinopathy

Curado Vilares Morgado,

Ferreira,

Santos-Silva

et al. 2023

Case Rep Ophthalmol

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The purpose of this clinical report was to describe a case of Cohen syndrome with its classical ophthalmological manifestations and novel VPS13B genetic variants. A 39-year-old Caucasian male patient with severe rod-cone retinal dystrophy and no history of parental consanguinity was referred to our ophthalmology department. Ophthalmologic history included high bilateral myopia and a 3-year prior bilateral cataract surgery. Systemic history included facial dysmorphism, intellectual disability, transient neutropenia, microcephaly, truncal obesity, and joint hyperextensibility. The patient presented classic fundoscopic features of pigmentary retinopathy in both eyes (OU). Optical coherence tomography (OCT) revealed bilateral central and diffuse retinal pigment epithelium (RPE) and outer retinal atrophy without concomitant macular edema, while fluorescein angiography (FA) demonstrated diffuse RPE atrophy with prominent choroidal vessels. The full-field ERG (ffERG) showed no dark-adapted or light-adapted responses and the P50 wave was not identified in the pattern ERG (pERG). The genetic study revealed two novel heterozygous variants in the VPS13B gene: (1) c.5138T>C p.(Leu1713Pro) and (2) c.10179del p.(Asn3393Lysfs*37), thus confirming the diagnosis of Cohen syndrome. This case report introduces these two novel genetic variants to the literature, in a patient with classic phenotypic characteristics of Cohen syndrome, a rare genetic disease which has been increasingly reported since its first description in 1973.

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“…CS is relatively common among Finnish population in spite of the low prevalence worldwide (5). Apart from this, CS has also been reported in Indian, Jordanian, Chinese, Saudi, Tunisian, Iranian, German, Syrian, Lebanese, and Pakistani (6)(7)(8)(9)(10)(11)(12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

A Novel Homozygous VPS13B Splice-Site Mutation Causing the Skipping of Exon 38 in a Chinese Family With Cohen Syndrome

Ji³

et al. 2021

Front. Pediatr.

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Background: Cohen syndrome (CS) is a clinically heterogeneous disorder characterized by extensive phenotypic variation with autosomal recessive inheritance. VPS13B was identified to be the disease-causing gene for CS. The objectives of the present study were to screen likely pathogenic mutations of the patient with developmental delay and mental retardation, and to determinate the effect of this splice-site mutation by reverse transcription analysis.Methods: Whole exome sequencing (WES) in combination with Sanger sequencing were performed to identify the causative mutations of this CS family. Subsequently, the impact of the intronic variant on splicing was analyzed by reverse transcription and the construction of expression vector.Results: A novel homozygous splice-site mutation (c.6940+1G>T) in the VPS13B gene was identified in this proband. Sanger sequencing analysis of the cDNA demonstrated that the c.6940+1G>T variant could cause the skipping of entire exon 38, resulting in the loss of 208 nucleotides and further give rise to the generation of a premature in-frame stop codon at code 2,247.Conclusions: The homozygous VPS13B splicing variant c.6940+1G>T was co-segregated with the CS phenotypes in this family and was identified to be the cause of CS after comprehensive consideration of the clinical manifestations, genetic analysis and cDNA sequencing result.

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Whole Exome Sequencing Identifies a Novel Homozygous Duplication Mutation in the VPS13B Gene in an Indian Family with Cohen Syndrome

Cited by 8 publications

References 14 publications

Identification of a Novel VPS13B Mutation in a Chinese Patient with Cohen Syndrome by Whole-Exome Sequencing

Identification of a Novel VPS13B Mutation in a Chinese Patient with Cohen Syndrome by Whole-Exome Sequencing

Cohen Syndrome: Novel VPS13B Genetic Variants in a Male Portuguese Patient with Pigmentary Retinopathy

A Novel Homozygous VPS13B Splice-Site Mutation Causing the Skipping of Exon 38 in a Chinese Family With Cohen Syndrome

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