Ancestral founder mutations in calpain-3 in the Indian Agarwal community: Historical, clinical, and molecular perspective

Research output: Contribution to journalArticle

Authors

  • Arunkanth Ankala
  • Jordan N. Kohn
  • Rashna Dastur
  • Pradnya Gaitonde
  • Satish V. Khadilkar
  • Madhuri R. Hegde

External Institution(s)

  • Emory University
  • Institute for Advanced Training and Research in Interdisciplinary Sciences
  • Sir J.J. Group of Hospitals

Details

Original languageEnglish (US)
Pages (from-to)931-937
Number of pages7
JournalMuscle and Nerve
Volume47
Issue number6
StatusPublished - Jun 2013
Peer-reviewedYes

Abstract

Introduction: Clinical heterogeneity of limb-girdle muscular dystrophies (LGMDs, 24 known subtypes), which includes overlapping phenotypes and varying ages of onset and morbidity, adds complexity to clinical and molecular diagnoses. Methods: To diagnose LGMD subtype, protein analysis, using immunohistochemistry (IHC) and immunoblotting, was followed by gene sequencing through a panel approach (simultaneous sequencing of known LGMD genes) in 9 patients from unrelated families of the Indian Agarwal community. Haplotype studies were performed by targeted SNP genotyping to establish mutation segregation. Results: We identified 2 founder mutations in CAPN3, a missense (c.2338G>C; p.D780H) and a splice-site (c.2099-1G>T) mutation, on 2 different haplotype backgrounds. The patients were either heterozygous for both or homozygous for either of these mutations. Conclusions: Founder mutations have immediate clinical application, at least in selected population groups. Clinically available gene panels may provide a definitive molecular diagnosis for heterogeneous disorders such as LGMD.

    Research areas

  • CAPN3, Founder mutation, Gene panel, LGMD2A, Limb-girdle muscular dystrophy, Splice-site mutation

Citation formats

APA

Ankala, A., Kohn, J. N., Dastur, R., Gaitonde, P., Khadilkar, S. V., & Hegde, M. R. (2013). Ancestral founder mutations in calpain-3 in the Indian Agarwal community: Historical, clinical, and molecular perspective. Muscle and Nerve, 47(6), 931-937. https://doi.org/10.1002/mus.23763

Harvard

Ankala, A, Kohn, JN, Dastur, R, Gaitonde, P, Khadilkar, SV & Hegde, MR 2013, 'Ancestral founder mutations in calpain-3 in the Indian Agarwal community: Historical, clinical, and molecular perspective', Muscle and Nerve, vol. 47, no. 6, pp. 931-937. https://doi.org/10.1002/mus.23763