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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

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Abstract

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.

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Authors and Affiliations

  1. Department of Neurology, National Institute of Mental Health and Neurosciences, Bangalore, India

    Kiran Polavarapu, Veeramani Preethish-Kumar, Seena Vengalil, Saraswati Nashi, Niranjan P. Mahajan, Muddasu Suhasini Keerthipriya, Chevula Pradeep-Chandra-Reddy, Sadanandavalli Retnaswami Chandra & Atchayaram Nalini

  2. Department of Clinical Neurosciences, National Institute of Mental Health and Neurosciences, Bangalore, India

    Kiran Polavarapu & Veeramani Preethish-Kumar

  3. Department of Molecular Genetics, National Institute of Mental Health and Neurosciences, Bangalore, India

    Deepha Sekar

  4. Department of Psychiatric Social Work, National Institute of Mental Health and Neurosciences, Bangalore, India

    Priya Treesa Thomas, Arun Sadasivan & Manjusha Warrier

  5. Department of Neurorehabilitation, National Institute of Mental Health and Neurosciences, Bangalore, India

    Anupam Gupta

  6. Department of Human Genetics, National Institute of Mental Health and Neurosciences, Bangalore, India

    Gautham Arunachal, Monojit Debnath & Swetha Gunasekaran

  7. Department of Neurophysiology, National Institute of Mental Health and Neurosciences, Bangalore, India

    Arpitha Puttegowda, Anu P. John, Ajitha Tavvala & Talakad N. Sathyaprabha

  8. Department of Pediatrics, Maastricht University Medical Center, Maastricht, The Netherlands

    Boris Kramer

  9. Department of Biomedical Engineering, Maastricht University Medical Center, Maastricht, The Netherlands

    Tammo Delhaas

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  1. Kiran Polavarapu
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Correspondence to Atchayaram Nalini.

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Polavarapu, K., Preethish-Kumar, V., Sekar, D. et al. 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. J Neurol 266, 2177–2185 (2019). https://doi.org/10.1007/s00415-019-09380-3

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