Whole Exome Sequencing Revealed a Novel GJB1 Pathogenic Variant and a Rare BSCL2 Mutation in Two Iranian Large Pedigrees with Multiple Affected Cases of Charcot-Marie-Tooth.

Content Provider	Europe PMC
Author	Mohsenpour, Neda Roknizadeh, Hassan Maghbooli, Mehdi Changi-Ashtiani, Majid Shahrooei, Mohammad Salehi, Mansoor Behnam, Mahdiyeh Shahani, Tina Biglari, Alireza
Abstract	Charcot-Marie-Tooth disease (CMT) is the most common hereditary neuropathy of the peripheral nervous system with a wide range of severity and age of onset. CMT patients share similar phenotypes which make it often impossible to identify the disease types based on clinical presentation and electrophysiological studies alone. In recent years, novel genetic diagnostic approaches such as whole exome sequencing (WES) has provided a ground for accurate diagnosis of CMT through identification of the disease-causing mutation(s). In the present study, that approach was effectively employed. Two unrelated large pedigrees with multiple affected cases of various pattern of inheritance (one autosomal dominant and one X-linked) were included. Clinical and electrophysiological data were obtained. DNA sample from each pedigree’s proband was subjected to WES. Data analysis was performed using an in-house developed pipeline, adopted from GATK and ANNOVAR. Candidate variant segregation was evaluated by PCR-based Sanger sequencing. A known but extremely rare (unreported in the Middle Easterners) mutation in BSCL2 (c.C269T:p.S90L) as well as a novel hemizygous variant in GJB1 (c.G224C:p.R75P) were identified and segregations were confirmed by Sanger sequencing. This study supports effectiveness of WES for genetic diagnosis of CMT in undiagnosed families.
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ISSN	22519637
Journal	International Journal of Molecular and Cellular Medicine [Int J Mol Cell Med]
Volume Number	8
PubMed Central reference number	PMC7241839
Issue Number	3
PubMed reference number	32489946
e-ISSN	22519645
DOI	10.22088/ijmcm.bums.8.3.169
Language	English
Publisher	Babol University of Medical Sciences
Publisher Date	2019-01-01
Publisher Place	Babol, Iran
Access Restriction	Open
Rights License	This is an Open Access article distributed under the terms of the Creative Commons Attribution License, (http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Subject Keyword	BSCL2 GJB1 whole exome sequencing Iranian Charcot-Marie-Tooth patients
Content Type	Text
Resource Type	Article
Subject	Cell Biology Genetics Molecular Biology Biochemistry Molecular Medicine Biotechnology