J Clin Neurol.  2017 Jan;13(1):91-97. 10.3988/jcn.2017.13.1.91.

Duchenne Muscular Dystrophy and Becker Muscular Dystrophy Confirmed by Multiplex Ligation-Dependent Probe Amplification: Genotype-Phenotype Correlation in a Large Cohort

• Vengalil S
• Preethish-Kumar V
• Polavarapu K
• Mahadevappa M
• Sekar D
• Purushottam M
• Thomas PT
• Nashi S
• Nalini A

• KMID: 2364903
• DOI: http://doi.org/10.3988/jcn.2017.13.1.91

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.

Keyword

Duchenne muscular dystrophy; Becker muscular dystrophy; genotype; phenotype

MeSH Terms

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
Dystrophin

Figure

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  Fig. 1 Frequencies of deletions of exons in DMD and BMD. BMD: Becker muscular dystrophy, DMD: Duchenne muscular dystrophy.

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  Fig. 2 Frequencies of duplications of exons in DMD and BMD. BMD: Becker muscular dystrophy, DMD: Duchenne muscular dystrophy.

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