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Mutational spectrum and phenotypic variability of Duchenne muscular dystrophy and related disorders in a Bangladeshi population

Lookup NU author(s): Dr Marc Woodbury-Smith

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).

Abstract

© 2023, The Author(s).Duchenne muscular dystrophy (DMD) is a severe rare neuromuscular disorder caused by mutations in the X-linked dystrophin gene. Several mutations have been identified, yet the full mutational spectrum, and their phenotypic consequences, will require genotyping across different populations. To this end, we undertook the first detailed genotype and phenotype characterization of DMD in the Bangladeshi population. We investigated the rare mutational and phenotypic spectrum of the DMD gene in 36 DMD-suspected Bangladeshi participants using an economically affordable diagnostic strategy involving initial screening for exonic deletions in the DMD gene via multiplex PCR, followed by testing PCR-negative patients for mutations using whole exome sequencing. The deletion mapping identified two critical DMD gene hotspot regions (near proximal and distal ends, spanning exons 8–17 and exons 45–53, respectively) that comprised 95% (21/22) of the deletions for this population cohort. From our exome analysis, we detected two novel pathogenic hemizygous mutations in exons 21 and 42 of the DMD gene, and novel pathogenic recessive and loss of function variants in four additional genes: SGCD, DYSF, COL6A3, and DOK7. Our phenotypic analysis showed that DMD suspected participants presented diverse phenotypes according to the location of the mutation and which gene was impacted. Our study provides ethnicity specific new insights into both clinical and genetic aspects of DMD.

Publication metadata

Author(s): Sarker S, Eshaque TB, Soorajkumar A, Nassir N, Zehra B, Kanta SI, Rahaman MA, Islam A, Akter S, Ali MK, Mim RA, Uddin KMF, Chowdhury MSJ, Shams N, Baqui MA, Lim ET, Akter H, Woodbury-Smith M, Uddin M

Publication type: Article

Publication status: Published

Journal: Scientific Reports

Year: 2023

Volume: 13

Issue: 1

Online publication date: 06/12/2023

Acceptance date: 02/12/2023

Date deposited: 19/12/2023

ISSN (electronic): 2045-2322

Publisher: Nature Research

URL: https://doi.org/10.1038/s41598-023-48982-w

DOI: 10.1038/s41598-023-48982-w

PubMed id: 38057384

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