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CC BY 4.0 · Glob Med Genet 2022; 09(01): 034-041
DOI: 10.1055/s-0041-1736567
Original Article

Disease Progression and Mutation Pattern in a Large Cohort of LGMD R1/LGMD 2A Patients from India

Valakunja H. Ganaraja‡   *
1   Department of Neurology, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India
,
Kiran Polavarapu‡   *
1   Department of Neurology, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India
2   Division of Neurology, Department of Medicine, Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, The Ottawa Hospital, Ottawa, Canada
,
Mainak Bardhan
1   Department of Neurology, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India
,
Veeramani Preethish-Kumar
1   Department of Neurology, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India
,
Shingavi Leena
1   Department of Neurology, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India
,
Ram M. Anjanappa
1   Department of Neurology, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India
2   Division of Neurology, Department of Medicine, Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, The Ottawa Hospital, Ottawa, Canada
,
Seena Vengalil
1   Department of Neurology, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India
,
Saraswati Nashi
1   Department of Neurology, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India
,
Gautham Arunachal
3   Department of Human Genetics, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India
,
Swetha Gunasekaran
3   Department of Human Genetics, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India
,
Dhaarini Mohan
1   Department of Neurology, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India
,
Sanita Raju
1   Department of Neurology, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India
,
Gopikrishnan Unnikrishnan
1   Department of Neurology, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India
,
Akshata Huddar
1   Department of Neurology, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India
,
Valasani Ravi-Kiran
1   Department of Neurology, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India
,
Priya T. Thomas
4   Department of Psychiatric Social Work, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India
,
Atchayaram Nalini
1   Department of Neurology, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India
› Institutsangaben Funding None.
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Abstract

Calpainopathy is caused by mutations in the CAPN3. There is only one clinical and genetic study of CAPN3 from India and none from South India. A total of 72 (male[M]:female [F] = 34:38) genetically confirmed probands from 72 independent families are included in this study. Consanguinity was present in 54.2%. The mean age of onset and duration of symptoms are 13.5 ± 6.4 and 6.3 ± 4.7 years, respectively. Positive family history occurred in 23.3%. The predominant initial symptoms were proximal lower limb weakness (52.1%) and toe walking (20.5%). At presentation, 97.2% had hip girdle weakness, 69.4% had scapular winging, and 58.3% had contractures. Follow-up was available in 76.4%, and 92.7% were ambulant at a mean age of 23.7 ± 7.6 years and duration of 4.5 years, remaining 7.3% became wheelchair-bound at 25.5 ± 5.7 years of age (mean duration = 13.5 ± 4.6), 4.1% were aged more than 40 years (duration range = 5–20). The majority remained ambulant 10 years after disease onset. Next-generation sequencing (NGS) detected 47 unique CAPN3 variants in 72 patients, out of which 19 are novel. Missense variants were most common occurring in 59.7% (homozygous = 29; Compound heterozygous = 14). In the remaining 29 patients (40.3%), at least one suspected loss of function variant was present. Common recurrent variants were c.2051–1G > T and c.2338G > C in 9.7%, c.1343G > A, c.802–9G > A, and c.1319G > A in 6.9% and c.1963delC in 5.5% of population. Large deletions were observed in 4.2%. Exon 10 mutations accounted for 12 patients (16.7%). Our study highlights the efficiency of NGS technology in screening and molecular diagnosis of limb-girdle muscular dystrophy with recessive form (LGMDR1) patients in India.

Keywords

CAPN3 - muscular dystrophy - LGMDR1 - next-generation sequencing

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.


* These two authors contributed equally to this work.


Supplementary Material



Publikationsverlauf

Eingereicht: 07. Juli 2021

Angenommen: 18. September 2021

Artikel online veröffentlicht:
09. November 2021

© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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