Please use this identifier to cite or link to this item: https://doi.org/10.1002/ajmg.c.31704
Title: Mutational spectrum of dystrophinopathies in Singapore: Insights for genetic diagnosis and precision therapy
Authors: Tomar, Swati 
Moorthy, Vikaesh
Sethi, Raman
Chai, Josiah
Low, Poh Sim 
Hong, Stacey Tay Kiat
Lai, Poh San 
Keywords: Science & Technology
Life Sciences & Biomedicine
Genetics & Heredity
Becker muscular dystrophy
Duchenne muscular dystrophy
dystrophinopathy
genetic diagnosis
mutation spectrum
DUCHENNE MUSCULAR-DYSTROPHY
DEPENDENT PROBE AMPLIFICATION
SPLICING ENHANCER SEQUENCE
PROTEIN TRUNCATION TEST
EXON-SKIPPING THERAPY
POINT MUTATIONS
NONSENSE MUTATION
MESSENGER-RNA
DMD GENE
MOLECULAR DIAGNOSIS
Issue Date: 1-Jun-2019
Publisher: WILEY
Citation: Tomar, Swati, Moorthy, Vikaesh, Sethi, Raman, Chai, Josiah, Low, Poh Sim, Hong, Stacey Tay Kiat, Lai, Poh San (2019-06-01). Mutational spectrum of dystrophinopathies in Singapore: Insights for genetic diagnosis and precision therapy. AMERICAN JOURNAL OF MEDICAL GENETICS PART C-SEMINARS IN MEDICAL GENETICS 181 (2) : 230-244. ScholarBank@NUS Repository. https://doi.org/10.1002/ajmg.c.31704
Abstract: © 2019 Wiley Periodicals, Inc. Duchenne and Becker muscular dystrophies (DMD/BMD) are X-linked recessive disorders caused by mutations in the DMD gene. Emerging therapies targeting patients with specific mutations are now becoming a reality for many of these patients. Precise molecular diagnosis is essential to facilitate the identification of possible new treatments for patients in the local context. In this study, we screened 145 dystrophinopathic patients in Singapore and assessed their molecular status for eligibility to current emerging genetic therapies. Overall, 140 (96.5%) of all patients harbored pathogenic DMD mutations comprising 95 exonic deletions (65.5%), 14 exonic duplications (9.7%), and 31 pathogenic small mutations (21.4%). Nonsense and frameshift mutations constitute 83.9% of all the small mutations. We found 71% (103/145) of all Singaporean dystrophinopathy patients to be theoretically amenable for exon skipping, either through skipping of single (53.1%) or multiple exons (17.9%). This approach is applicable to 81.1% (77/95) of patients carrying deletions and 83.9% (26/31) of those with small mutations. Eteplirsen induced skipping of exon 51 is applicable to 12.4% of local patients. Nonsense read-through therapy was found to be applicable in another 12.4% of all patients. Mutation screening is crucial for providing insights into the underlying genetic signature of the disease in the local population and contributes toward existing information on DMD mutations in Asia and globally. This will guide future targeted drug development and clinical trial planning for this disease.
Source Title: AMERICAN JOURNAL OF MEDICAL GENETICS PART C-SEMINARS IN MEDICAL GENETICS
URI: https://scholarbank.nus.edu.sg/handle/10635/173674
ISSN: 15524868
15524876
DOI: 10.1002/ajmg.c.31704
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