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

Sarker, Shaoli
Eshaque, Tamannyat Binte
Soorajkumar, Anjana
Nassir, Nasna
Zehra, Binte
Kanta, Shayla Imam
Rahaman, Md Atikur
Islam, Amirul
Akter, Shimu
Ali, Mohammad Kawsar
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Abstract

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.

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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. Mutational spectrum and phenotypic variability of Duchenne muscular dystrophy and related disorders in a Bangladeshi population. Sci Rep. 2023 Dec 6;13(1):21547. doi: 10.1038/s41598-023-48982-w. PMID: 38057384; PMCID: PMC10700514.

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10.1038/s41598-023-48982-w
PubMed ID
38057384
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Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creativecommons. org/ licenses/ by/4. 0/. © The Author(s) 2023Attribution 4.0 International