title: Duchenne Muscular Dystrophy and Becker Muscular Dystrophy Confirmed by Multiplex Ligation-Dependent Probe Amplification: Genotype-Phenotype Correlation in a Large Cohort.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Neurology, National Institute of Mental Health and Neurosciences, Bangalore, India.
authors.forename: Seena
authors.initials: S
authors.lastname: Vengalil
authors.affiliation: Department of Clinical Neurosciences, National Institute of Mental Health and Neurosciences, Bangalore, India.
authors.forename: Veeramani
authors.initials: V
authors.lastname: Preethish-Kumar
authors.affiliation: Department of Clinical Neurosciences, National Institute of Mental Health and Neurosciences, Bangalore, India.
authors.forename: Kiran
authors.initials: K
authors.lastname: Polavarapu
authors.affiliation: Department of Neurology, National Institute of Mental Health and Neurosciences, Bangalore, India.
authors.forename: Manjunath
authors.initials: M
authors.lastname: Mahadevappa
authors.affiliation: Department of Molecular Genetics, National Institute of Mental Health and Neurosciences, Bangalore, India.
authors.forename: Deepha
authors.initials: D
authors.lastname: Sekar
authors.affiliation: Department of Molecular Genetics, National Institute of Mental Health and Neurosciences, Bangalore, India.
authors.forename: Meera
authors.initials: M
authors.lastname: Purushottam
authors.affiliation: Department of Psychiatric Social Work, National Institute of Mental Health and Neurosciences, Bangalore, India.
authors.forename: Priya Treesa
authors.initials: PT
authors.lastname: Thomas
authors.affiliation: Department of Neurology, National Institute of Mental Health and Neurosciences, Bangalore, India.
authors.forename: Saraswathi
authors.initials: S
authors.lastname: Nashi
authors.affiliation: Department of Neurology, National Institute of Mental Health and Neurosciences, Bangalore, India. atchayaramnalini@yahoo.co.in.
authors.forename: Atchayaram
authors.initials: A
authors.lastname: Nalini
keywords: Becker muscular dystrophy; Duchenne muscular dystrophy; genotype; phenotype