Sie befinden Sich nicht im Netzwerk der Universität Paderborn. Der Zugriff auf elektronische Ressourcen ist gegebenenfalls nur via VPN oder Shibboleth (DFN-AAI) möglich. mehr Informationen...
Ancestral founder mutations in calpain-3 in the Indian Agarwal community: Historical, clinical, and molecular perspective
Ist Teil von
Muscle & nerve, 2013-06, Vol.47 (6), p.931-937
Ort / Verlag
United States: Blackwell Publishing Ltd
Erscheinungsjahr
2013
Quelle
Wiley-Blackwell Journals
Beschreibungen/Notizen
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. Muscle Nerve 47: 931–937, 2013