Duchenne Muscular Dystrophy and Becker Muscular Dystrophy Confirmed by Multiplex Ligation-Dependent Probe Amplification: Genotype-Phenotype Correlation in a Large Cohort.
- Author:
Seena VENGALIL
1
;
Veeramani PREETHISH-KUMAR
;
Kiran POLAVARAPU
;
Manjunath MAHADEVAPPA
;
Deepha SEKAR
;
Meera PURUSHOTTAM
;
Priya Treesa THOMAS
;
Saraswathi NASHI
;
Atchayaram NALINI
Author Information
- Publication Type:Original Article
- Keywords: Duchenne muscular dystrophy; Becker muscular dystrophy; genotype; phenotype
- MeSH: Child; Cohort Studies*; Dystrophin; Exons; Genetic Association Studies*; Genotype; Humans; India; Multiplex Polymerase Chain Reaction*; Muscular Dystrophy, Duchenne*; Phenotype; Reading Frames; Referral and Consultation; Retrospective Studies; Wheelchairs
- From:Journal of Clinical Neurology 2017;13(1):91-97
- CountryRepublic of Korea
- Language:English
- Abstract: BACKGROUND AND PURPOSE: Studies of cases of Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) confirmed by multiplex ligation-dependent probe amplification (MLPA) have determined the clinical characteristics, genotype, and relations between the reading frame and phenotype for different countries. This is the first such study from India. METHODS: A retrospective genotype-phenotype analysis of 317 MLPA-confirmed patients with DMD or BMD who visited the neuromuscular clinic of a quaternary referral center in southern India. RESULTS: The 317 patients comprised 279 cases of DMD (88%), 32 of BMD (10.1%), and 6 of intermediate phenotype (1.9%). Deletions accounted for 91.8% of cases, with duplications causing the remaining 8.2%. There were 254 cases of DMD (91%) with deletions and 25 (9%) due to duplications, and 31 cases (96.8%) of BMD with deletions and 1 (3.2%) due to duplication. All six cases of intermediate type were due to deletions. The most-common mutation was a single-exon deletion. Deletions of six or fewer exons constituted 68.8% of cases. The deletion of exon 50 was the most common. The reading-frame rule held in 90% of DMD and 94% of BMD cases. A tendency toward a lower IQ and earlier wheelchair dependence was observed with distal exon deletions, though a significant correlation was not found. CONCLUSIONS: The reading-frame rule held in 90% to 94% of children, which is consistent with reports from other parts of the world. However, testing by MLPA is a limitation, and advanced sequencing methods including analysis of the structure of mutant dystrophin is needed for more-accurate assessments of the genotype-phenotype correlation.
