A Novel VPS13B Mutation Identified by Whole-Exome Sequencing in Iranian Patients with Cohen Syndrome

Karimzadeh, Mohammad Reza; Omidi, Fatemeh; Sahebalzamani, Afsaneh; Saeidi, Kolsoum

doi:10.1007/s12031-021-01852-4

Cited by 3 publications

(3 citation statements)

References 41 publications

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“…2, the VPS13B protein comprised of six conserved domains as follows: a Chorein/VPS13 region at the very Nterminus that forms the leucine zipper (aa 3-102, pfam12624), a second VPS13-N-terminal region (aa 139-280, pfam16908), a SHR-binding domain, aa 2603-2702), an extended SHR -binding domain (aa 2715-3363, pfam06650), a VPS13-C-terminal region (aa 3543-3709, pfam16909), and an autophagyrelated protein C terminal domain (aa 3713-3816, pfam09333) (36). furthermore, a possible vacuolar targeting motif (aa 1518-1521) and two peroxisomal matrix protein targeting signals, one near the Nterminus (aa 263-271) and the other near the C-terminus (aa 3553-3561), are also predicted (9). The results of multiple alignment for the corresponding sequence revealed that the c.1043G > A (p.W348X) mutation occurs in a region near the second VPS13-N-terminal region so that the resulting protein would contain only two out of six above-mentioned domains.…”

Section: Resultsmentioning

confidence: 99%

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Cohen syndrome due to a novel stop-gain mutation in VPS13B gene: A case report and comparative study in affected siblings worldwide

Saeediye,

Parvini

2024

Preprint

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Background Cohen syndrome (CS) is a highly rare heterogeneous disorder associated with mutations in the vacuolar protein sorting 13 homolog B (VPS13B) gene. CS is mainly characterized by intellectual disability, microcephaly, progressive retinopathy, hypotonia, obesity, neutropenia and dysmorphic facial features. Case presentation : Here, we report two affected siblings suspicious to CS. Our objectives were the delineation of gene mutation causing this rare condition and comparison of observed manifestations with symptoms reported in other CS affected siblings worldwide. Whole exome sequencing (WES) in combination with Sanger sequencing were utilized to identify the disease-causing mutation in the affected siblings. Subsequently, to elucidate the effects of the mutation found, clinical data of patients were collected. Moreover, the possible impact of the identified mutation on the corresponding protein was analyzed using bioinformatics tools. A novel homozygous stop-gain mutation NM_015243: c.1043G > A: p.W348X in the VPS13B gene was identified in the proband. This mutation was confirmed by Sanger sequencing in the affected siblings and segregated with the autosomal recessive (AR) inheritance pattern of CS. Moreover, in-silico approaches highly confirmed the disease-causing nature of the identified mutation. Conclusion Our findings could expand the mutations spectrum of CS and the comparative study of all reported manifestations in CS affected siblings throughout the world, clearly shed light the common and uncommon manifestations of CS in different affected siblings with different VPS13B gene mutations. These results could be also useful in genetic diagnosis and counseling in CS affected patients.

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Section: Resultsmentioning

confidence: 99%

“…gene=VPS13B). The reported cases are from different countries including India (1), Finland (4), Turkey, Belgium, Italy, Germany, France (7), Tunisia (8) and Iran (9,10).…”

Section: Introductionmentioning

confidence: 99%

Cohen syndrome due to a novel stop-gain mutation in VPS13B gene: A case report and comparative study in affected siblings worldwide

Saeediye,

Parvini

2024

Preprint

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“…[1][2][3][4] Cohen syndrome is caused by a variant or a massive genomic rearrangement of the autosomal 8q22.2 vacuolar protein sorting 13 homolog B (VPS13B) gene, and the VPS13B gene is the only gene responsible for Cohen syndrome. 2,5 So far, approximately 1000 cases of Cohen syndrome have been reported at home and abroad of which five cases have been genetically diagnosed in China. [6][7][8][9][10] In the present study, the clinical data of a child with Cohen syndrome diagnosed using genetic diagnosis were reviewed to retrieve the relevant literature to explore the clinical and genetic variation characteristics of Cohen syndrome.…”

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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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Deletion as novel variants in VPS13B gene in Cohen syndrome: Case series

Kang,

Ma,

Zhao

2023

Translational Neuroscience

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Background Cohen syndrome (OMIM No. # 216550) is a rare autosomal recessive disorder caused by homozygous mutation in the vacuolar protein sorting 13 homolog B (VPS13B) gene on chromosome 8q22.2. Clinical manifestations include hypermobile joints, microcephaly, intellectual disabilities, craniofacial and limb anomalies, and neutropenia. To date, more than 200 mutations of VPS13B have been reported in over 1,000 Cohen syndrome patients. This article reviews the clinical data of two cases of Cohen syndrome diagnosed by whole exome sequencing. Results Both children visited for psychomotor retardation. Gene detection showed a mutation in 8q22.2, NM_017890.4 Intron38 c.6940+1G > T and heterozygotic deletion of exon 3-19 of the VPS13B gene (Case 1), and a mutation in 8q22.2, NM_017890.4 Intron38 c.6940+1G > T and 8q22, NM_017890.4 Exon56 c10334_10335del in the VPS13B gene (Case 2). The variation was predicted to be pathogenic by related software, and they have not been reported. Conclusion Cohen syndrome should be considered in the differential diagnosis of any child with developmental retardation and neutropenia. The present study increases the mutation spectrum of the VPS13B gene and could be helpful in genetic diagnosis and genetic counseling in Cohen syndrome patients.

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A Novel VPS13B Mutation Identified by Whole-Exome Sequencing in Iranian Patients with Cohen Syndrome

Cited by 3 publications

References 41 publications

Cohen syndrome due to a novel stop-gain mutation in VPS13B gene: A case report and comparative study in affected siblings worldwide

Cohen syndrome due to a novel stop-gain mutation in VPS13B gene: A case report and comparative study in affected siblings worldwide

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

Deletion as novel variants in VPS13B gene in Cohen syndrome: Case series

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