Identification of a novel DMD duplication identified by a combination of MLPA and targeted exome sequencing

Abstract

BackgroundDuchenne muscular dystrophy (DMD) is an X-linked recessive muscle-wasting disease caused by a mutation in the DMD gene. The aim of this study was to identify a de novo mutation of the DMD gene in the family of a 9-month-old Chinese male patient, as well as to describe the phenotypic characteristics of this patient.ResultsThe patient was suspected to suffer from DMD according to physical examination, biochemical analyses, and electromyogram. We identified a duplication of exons 4–42 in DMD gene with targeted exome sequencing and multiplex ligation-dependent probe amplification (MLPA). In addition, the patient’s mother was a carrier of the same mutation.ConclusionsWe identified a de novo duplication of exons 4–42 in a patient with early stage DMD. The discovery of this mutation may provide insights into future investigations.

Mutation spectrum analysis of Duchenne/Becker muscular dystrophy in 68 families in Kuwait: The era of personalized medicine

“…A total of 35 different large rearrangements, 2 deletion-insertions and 4 substitution mutations were identified in 68 unrelated individuals. The deletion and duplication rates were 66.2% and 4.4%, respectively, which is consistent with reports from other parts of the world [ 8 , 13 , 20 ], except in Taiwanese, Bulgarian and Egyptian populations where the duplication rates were 24.7%, 27% and 27.8%, respectively [ 6 , 21 , 22 ].…”

“…Deletions of exons outside the usual hotspots, duplications and carrier analysis often prevent a precise genetic diagnosis when using mPCR alone. Currently, multiplex ligation-dependent probe amplification (MLPA) has been effectively used for the accurate detection of deletions and duplications in DMD/BMD-affected males and female carriers [ 20 , 31 – 34 ]. Using this diagnostic approach, we managed to clarify the disease-causing mutations in 70.6% of DMD/BMD probands and determined the deletion/duplication borders in all the cases.…”

Clinical and Molecular Diagnosis in Muscular Dystrophies

“…A large number of research studies highlight the utility of MLPA as detection methods for DMD gene [84][85][86] which is the largest gene (2.2 Mb) of the human genome.…”

Molecular Diagnosis of Muscular Dystrophy Patients in Western Indian Population: A Comprehensive Mutation Analysis Using Amplicon Sequencing

“…Duchenne Muscular Dystrophy (OMIM # 310200) is the most common, rapidly progressive, and severe neuromuscular disease. It inherits in an X-linked recessive manner affecting 1 in 3,500 male children with onset before 5 years’ age ( Wu et al, 2017 ; Mohammed et al, 2018 ; Zhang Y. et al, 2019 ). Becker Muscular Dystrophy (BMD) is a less severe form of the disease caused by the mutation in the DMD gene and slow progressive with an incidence rate of 1 in 20,000 male children ( Aartsma-Rus et al, 2016 ; Wu et al, 2017 ; Mohammed et al, 2018 ; Kong et al, 2019 ; Wang et al, 2019 ).…”

“…It inherits in an X-linked recessive manner affecting 1 in 3,500 male children with onset before 5 years’ age ( Wu et al, 2017 ; Mohammed et al, 2018 ; Zhang Y. et al, 2019 ). Becker Muscular Dystrophy (BMD) is a less severe form of the disease caused by the mutation in the DMD gene and slow progressive with an incidence rate of 1 in 20,000 male children ( Aartsma-Rus et al, 2016 ; Wu et al, 2017 ; Mohammed et al, 2018 ; Kong et al, 2019 ; Wang et al, 2019 ). The DMD (dystrophin) is a large gene encompassing 79 exons and spanning approximately 2.5 Mb of the genomic DNA.…”