Isfahan University of Medical Sciences

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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 Publisher



Mohsenpour N1 ; Roknizadeh H2 ; Maghbooli M3 ; Changiashtiani M4 ; Shahrooei M5, 6 ; Salehi M7, 8 ; Behnam M7 ; Shahani T1 ; Biglari A1
Authors

Source: International Journal of Molecular and Cellular Medicine Published:2019


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. © 2019, Babol University of Medical Sciences.
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