Universität zu Köln

Hashmi, Jamil A., Fadhli, Fatima, Almatrafi, Ahmed, Afzal, Sibtain, Ramzan, Khushnooda, Thiele, Holger ORCID: 0000-0002-0169-998X, Nuernberg, Peter and Basit, Sulman ORCID: 0000-0003-4294-6825 (2020). Homozygosity mapping and whole exome sequencing provide exact diagnosis of Cohen syndrome in a Saudi family. Brain Dev., 42 (8). S. 587 - 594. AMSTERDAM: ELSEVIER. ISSN 1872-7131

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Abstract

Background: Cohen syndrome (CS) is a rare multi-system autosomal recessive disorder with a high prevalence in the Finnish population. Clinical features of Finnish-type CS are homogeneous, however, in non-Finnish populations, CS diagnosis is challenging due to broad phenotypic variability. Methods: We studied a consanguineous family having three affected individuals with clinical features of severe intellectual disability and global developmental delay. Clinical diagnosis of the phenotype could not be established based on the features. Therefore, whole genome SNP genotyping and whole exome sequencing (WES) were performed on DNA samples from affected and unaffected family members. Results: Homozygosity mapping identified a shared loss of heterozygosity region on chromosome 8q22.1-q22.3 and WES data analysis revealed an insertion-deletion (indel) mutation (c.11519_11521delCAAinsT) in the VPS13B gene. The indel is predicted to cause a frameshift resulting in a premature termination of the VPS13B protein (NP_060360.3:p.Pro3840Leufs*2). Conclusion: VPS13B encodes a giant transmembrane protein called vacuolar protein sorting 13 homolog B. VPS13B is known to play a role in the glycosylation of Golgi proteins and in endosomal-lysosomal trafficking. Moreover, it is thought to function in vesicle mediated transport and sorting of proteins within the cell. The mechanism by which abnormalities of the VPS13B protein lead to the phenotype of CS is currently unknown. Here, in this study, we successfully established a clinical diagnosis of CS cases from a family using genomic analyses. Clinical re-examination of the patients revealed characteristic ocular abnormalities. (C) 2020 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Hashmi, Jamil A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Fadhli, Fatima UNSPECIFIED UNSPECIFIED UNSPECIFIED Almatrafi, Ahmed UNSPECIFIED UNSPECIFIED UNSPECIFIED Afzal, Sibtain UNSPECIFIED UNSPECIFIED UNSPECIFIED Ramzan, Khushnooda UNSPECIFIED UNSPECIFIED UNSPECIFIED Thiele, Holger UNSPECIFIED orcid.org/0000-0002-0169-998X UNSPECIFIED Nuernberg, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Basit, Sulman UNSPECIFIED orcid.org/0000-0003-4294-6825 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-322229
DOI:	10.1016/j.braindev.2020.04.010
Journal or Publication Title:	Brain Dev.
Volume:	42
Number:	8
Page Range:	S. 587 - 594
Date:	2020
Publisher:	ELSEVIER
Place of Publication:	AMSTERDAM
ISSN:	1872-7131
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SYNDROME-ASSOCIATED PROTEIN; NATURAL-HISTORY; GENE; MUTATIONS; FINNISH Multiple languages Clinical Neurology; Pediatrics Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/32222