This work was supported by the Muscular Dystrophy Association (MDA138896 to M.R.H.).
Case of the Month
Ancestral founder mutations in calpain-3 in the Indian Agarwal community: Historical, clinical, and molecular perspective
Article first published online: 10 MAY 2013
Copyright © 2012 Wiley Periodicals, Inc.
Muscle & Nerve
Volume 47, Issue 6, pages 931–937, June 2013
How to Cite
Ankala, A., Kohn, J. N., Dastur, R., Gaitonde, P., Khadilkar, S. V. and Hegde, M. R. (2013), Ancestral founder mutations in calpain-3 in the Indian Agarwal community: Historical, clinical, and molecular perspective. Muscle Nerve, 47: 931–937. doi: 10.1002/mus.23763
- Issue published online: 23 MAY 2013
- Article first published online: 10 MAY 2013
- Accepted manuscript online: 24 DEC 2012 04:48AM EST
- Manuscript Accepted: 14 DEC 2012
Vol. 48, Issue 6, 999, Article first published online: 7 OCT 2013
- founder mutation;
- gene panel;
- limb-girdle muscular dystrophy;
- splice-site mutation
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.
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.
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.
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. Muscle Nerve 47: 931–937, 2013