Mutation pattern in 606 Duchenne muscular dystrophy children with a comparison between familial and non-familial forms: a study in an Indian large single-center cohort

Kiran Polavarapu, Veeramani Preethish-Kumar, Deepha Sekar, Seena Vengalil, Saraswati Nashi, Niranjan P. Mahajan, Priya Treesa Thomas, Arun Sadasivan, Manjusha Warrier, Anupam Gupta, Gautham Arunachal, Monojit Debnath, Muddasu Suhasini Keerthipriya, Chevula Pradeep-Chandra-Reddy, Arpitha Puttegowda, Anu P. John, Ajitha Tavvala, Swetha Gunasekaran, Talakad N. Sathyaprabha, Sadanandavalli Retnaswami ChandraBoris Kramer, Tammo Delhaas, Atchayaram Nalini*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Introduction Duchenne muscular dystrophy (DMD) is induced by a wide spectrum of mutations such as exon deletions, duplications and small mutations in the dystrophin gene. This is the first study on the mutational spectrum in a cohort of DMD children from India, with an emphasis to compare the mutations in familial and sporadic forms. Results Multiplex ligation-dependent probe amplification (MLPA) and next-generation sequencing (NGS) identified 525 and 70 cases of DMD, respectively, while 11 cases showed absent dystrophin staining with no mutations detected. Families with two or more affected males contributed to 12% of the entire cohort. The mutations comprised of exonic deletions in 492/606 (81.2%), duplications in 33/606 (5.4%) and small mutations (point mutations and INDELs) in 70/606 (11.5%) cases. MLPA identified significantly more larger mutations in sporadic (88.2%) than in familial cases (75.3%). The mutations in NGS were: [nonsense = 40 (57.1%); frameshift = 17 (24.3%); splice variant = 12 (17.1%)]. Nonsense mutations were more common in familial than in sporadic cases: 17.8% vs 10.7%. The familial group reported an earlier onset of disease (2.8 +/- 1.7 years) as compared to sporadic cases (3.8 +/- 1.6 years). Conclusion MLPA could identify mutations in a high percentage of our DMD children. The preponderance of small mutations was noted to be distinctly higher in the familial group. Intriguingly, the familial form of DMD formed a small percentage of the entire cohort. The reasons could be increasing awareness among parents and physicians with early identification of DMD cases, genetic counseling and prenatal testing.

Original languageEnglish
Pages (from-to)2177-2185
Number of pages9
JournalJournal of Neurology
Issue number9
Publication statusPublished - Sept 2019


  • Duchenne muscular dystrophy
  • Familial
  • Mutation
  • India

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