Mutational spectrum and phenotypic variability of Duchenne muscular dystrophy and related disorders in a Bangladeshi population
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. T...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-12-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-48982-w |
| _version_ | 1827590650091012096 |
|---|---|
| author | Shaoli Sarker Tamannyat Binte Eshaque Anjana Soorajkumar Nasna Nassir Binte Zehra Shayla Imam Kanta Md Atikur Rahaman Amirul Islam Shimu Akter Mohammad Kawsar Ali Rabeya Akter Mim K. M. Furkan Uddin Mohammod Shah Jahan Chowdhury Nusrat Shams Md. Abdul Baqui Elaine T. Lim Hosneara Akter Marc Woodbury-Smith Mohammed Uddin |
| author_facet | Shaoli Sarker Tamannyat Binte Eshaque Anjana Soorajkumar Nasna Nassir Binte Zehra Shayla Imam Kanta Md Atikur Rahaman Amirul Islam Shimu Akter Mohammad Kawsar Ali Rabeya Akter Mim K. M. Furkan Uddin Mohammod Shah Jahan Chowdhury Nusrat Shams Md. Abdul Baqui Elaine T. Lim Hosneara Akter Marc Woodbury-Smith Mohammed Uddin |
| author_sort | Shaoli Sarker |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T01:19:47Z |
| format | Article |
| id | doaj.art-b12c0b69d34d43fc96da4a42d0764a7d |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-09T01:19:47Z |
| publishDate | 2023-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-b12c0b69d34d43fc96da4a42d0764a7d2023-12-10T12:15:30ZengNature PortfolioScientific Reports2045-23222023-12-0113111110.1038/s41598-023-48982-wMutational spectrum and phenotypic variability of Duchenne muscular dystrophy and related disorders in a Bangladeshi populationShaoli Sarker0Tamannyat Binte Eshaque1Anjana Soorajkumar2Nasna Nassir3Binte Zehra4Shayla Imam Kanta5Md Atikur Rahaman6Amirul Islam7Shimu Akter8Mohammad Kawsar Ali9Rabeya Akter Mim10K. M. Furkan Uddin11Mohammod Shah Jahan Chowdhury12Nusrat Shams13Md. Abdul Baqui14Elaine T. Lim15Hosneara Akter16Marc Woodbury-Smith17Mohammed Uddin18Genetics and Genomic Medicine Centre (GGMC), NeuroGen HealthcareGenetics and Genomic Medicine Centre (GGMC), NeuroGen HealthcareCenter for Applied and Translational Genomics (CATG), Mohammed Bin Rashid University of Medicine and Health SciencesCenter for Applied and Translational Genomics (CATG), Mohammed Bin Rashid University of Medicine and Health SciencesCenter for Applied and Translational Genomics (CATG), Mohammed Bin Rashid University of Medicine and Health SciencesBangladesh Shishu Hospital and InstituteGenetics and Genomic Medicine Centre (GGMC), NeuroGen HealthcareGenetics and Genomic Medicine Centre (GGMC), NeuroGen HealthcareGenetics and Genomic Medicine Centre (GGMC), NeuroGen HealthcareGenetics and Genomic Medicine Centre (GGMC), NeuroGen HealthcareGenetics and Genomic Medicine Centre (GGMC), NeuroGen HealthcareGenetics and Genomic Medicine Centre (GGMC), NeuroGen HealthcareGenetics and Genomic Medicine Centre (GGMC), NeuroGen HealthcareGenetics and Genomic Medicine Centre (GGMC), NeuroGen HealthcareDepartment of Biochemistry, Holy Family Red Crescent Medical College and HospitalDepartment of Genomics and Computational Biology, University of Massachusetts Chan Medical SchoolGenetics and Genomic Medicine Centre (GGMC), NeuroGen HealthcareBiosciences Institute, Newcastle UniversityCenter for Applied and Translational Genomics (CATG), Mohammed Bin Rashid University of Medicine and Health SciencesAbstract 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.https://doi.org/10.1038/s41598-023-48982-w |
| spellingShingle | Shaoli Sarker Tamannyat Binte Eshaque Anjana Soorajkumar Nasna Nassir Binte Zehra Shayla Imam Kanta Md Atikur Rahaman Amirul Islam Shimu Akter Mohammad Kawsar Ali Rabeya Akter Mim K. M. Furkan Uddin Mohammod Shah Jahan Chowdhury Nusrat Shams Md. Abdul Baqui Elaine T. Lim Hosneara Akter Marc Woodbury-Smith Mohammed Uddin Mutational spectrum and phenotypic variability of Duchenne muscular dystrophy and related disorders in a Bangladeshi population Scientific Reports |
| title | Mutational spectrum and phenotypic variability of Duchenne muscular dystrophy and related disorders in a Bangladeshi population |
| title_full | Mutational spectrum and phenotypic variability of Duchenne muscular dystrophy and related disorders in a Bangladeshi population |
| title_fullStr | Mutational spectrum and phenotypic variability of Duchenne muscular dystrophy and related disorders in a Bangladeshi population |
| title_full_unstemmed | Mutational spectrum and phenotypic variability of Duchenne muscular dystrophy and related disorders in a Bangladeshi population |
| title_short | Mutational spectrum and phenotypic variability of Duchenne muscular dystrophy and related disorders in a Bangladeshi population |
| title_sort | mutational spectrum and phenotypic variability of duchenne muscular dystrophy and related disorders in a bangladeshi population |
| url | https://doi.org/10.1038/s41598-023-48982-w |
| work_keys_str_mv | AT shaolisarker mutationalspectrumandphenotypicvariabilityofduchennemusculardystrophyandrelateddisordersinabangladeshipopulation AT tamannyatbinteeshaque mutationalspectrumandphenotypicvariabilityofduchennemusculardystrophyandrelateddisordersinabangladeshipopulation AT anjanasoorajkumar mutationalspectrumandphenotypicvariabilityofduchennemusculardystrophyandrelateddisordersinabangladeshipopulation AT nasnanassir mutationalspectrumandphenotypicvariabilityofduchennemusculardystrophyandrelateddisordersinabangladeshipopulation AT bintezehra mutationalspectrumandphenotypicvariabilityofduchennemusculardystrophyandrelateddisordersinabangladeshipopulation AT shaylaimamkanta mutationalspectrumandphenotypicvariabilityofduchennemusculardystrophyandrelateddisordersinabangladeshipopulation AT mdatikurrahaman mutationalspectrumandphenotypicvariabilityofduchennemusculardystrophyandrelateddisordersinabangladeshipopulation AT amirulislam mutationalspectrumandphenotypicvariabilityofduchennemusculardystrophyandrelateddisordersinabangladeshipopulation AT shimuakter mutationalspectrumandphenotypicvariabilityofduchennemusculardystrophyandrelateddisordersinabangladeshipopulation AT mohammadkawsarali mutationalspectrumandphenotypicvariabilityofduchennemusculardystrophyandrelateddisordersinabangladeshipopulation AT rabeyaaktermim mutationalspectrumandphenotypicvariabilityofduchennemusculardystrophyandrelateddisordersinabangladeshipopulation AT kmfurkanuddin mutationalspectrumandphenotypicvariabilityofduchennemusculardystrophyandrelateddisordersinabangladeshipopulation AT mohammodshahjahanchowdhury mutationalspectrumandphenotypicvariabilityofduchennemusculardystrophyandrelateddisordersinabangladeshipopulation AT nusratshams mutationalspectrumandphenotypicvariabilityofduchennemusculardystrophyandrelateddisordersinabangladeshipopulation AT mdabdulbaqui mutationalspectrumandphenotypicvariabilityofduchennemusculardystrophyandrelateddisordersinabangladeshipopulation AT elainetlim mutationalspectrumandphenotypicvariabilityofduchennemusculardystrophyandrelateddisordersinabangladeshipopulation AT hosnearaakter mutationalspectrumandphenotypicvariabilityofduchennemusculardystrophyandrelateddisordersinabangladeshipopulation AT marcwoodburysmith mutationalspectrumandphenotypicvariabilityofduchennemusculardystrophyandrelateddisordersinabangladeshipopulation AT mohammeduddin mutationalspectrumandphenotypicvariabilityofduchennemusculardystrophyandrelateddisordersinabangladeshipopulation |