Open AccessNext-Generation Sequencing in a Cohort of Asian Indian Patients with the Duchenne Muscular Dystrophy Phenotype: Diagnostic Yield and Mutation Spectrum
Author(s) -
Gayatri Nerakh,
Prajnya Ranganath,
Sakthivel Murugan
Publication year - 2020
Publication title -
journal of pediatric genetics
Language(s) - English
Resource type - Journals
eISSN - 2146-4596
pISSN - 2146-460X
DOI - 10.1055/s-0040-1713850
Subject(s) - multiplex ligation dependent probe amplification , duchenne muscular dystrophy , muscular dystrophy , exome sequencing , genetics , proband , phenotype , medicine , bioinformatics , mutation , biology , gene , exon
Multiplex ligation-dependent probe amplification (MLPA) detects exonic deletions and duplications in the DMD gene in around 65 to 70% of patients with the Duchenne muscular dystrophy (DMD) phenotype. This study looks at the diagnostic yield of next-generation sequencing (NGS) and the mutation spectrum in an Asian Indian cohort of MLPA-negative cases with the DMD phenotype. NGS-based sequencing of DMD gene was done in 28 MLPA-negative cases (25 male probands with the DMD phenotype and 3 obligate carrier mothers of deceased affected male patients) and disease-causing variants were identified in 19 (67.9%) of these cases. Further molecular testing in four of the remaining nine cases revealed gene variants associated with limb girdle muscular dystrophies. Thus, NGS-based multigene panel testing for muscular dystrophy-associated genes or clinical exome sequencing rather than targeted DMD gene sequencing appears to be a more cost-effective testing modality with better diagnostic yield, for MLPA-negative patients with the DMD phenotype.