Ancestral founder mutations in calpain‐3 in the Indian Agarwal community: Historical, clinical, and molecular perspective. Issue 6 (11th May 2013)

• Record Type: Journal Article
• Authors: Ankala, Arunkanth; Kohn, Jordan N.; Dastur, Rashna; Gaitonde, Pradnya; Khadilkar, Satish V.; Hegde, Madhuri R.
• Is Part Of: Muscle & nerve. Volume 47:Issue 6(2013:Jun.)
• Page Start: 931
• Page End: 937
• Publication Date: 2013-05-11
• Subjects: Neuromuscular diseases -- Periodicals; Muscles -- Periodicals; Nerves -- Periodicals; 616.74
• DOI: 10.1002/mus.23763
• Languages: English
• ISSNs: 0148-639X

Abstract

<abstract abstract-type="main"> <title>ABSTRACT</title> <sec id="mus23763-sec-0001" sec-type="section"> <title>Introduction</title> <p>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.</p> </sec> <sec id="mus23763-sec-0002" sec-type="section"> <title>Methods</title> <p>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.</p> </sec> <sec id="mus23763-sec-0003" sec-type="section"> <title>Results</title> <p>We identified 2 founder mutations in <italic>CAPN3</italic>, 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.</p> </sec> <sec id="mus23763-sec-0004" sec-type="section"> <title>Conclusions</title> <p>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</p> </sec> </abstract>