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Muscle pathology in 31 patients with calpain 3 gene mutations
Affiliations- 1 Department of Neurology, Institute of Psychiatry and Neurology, Warsaw, Poland
- Centre de Référence des Maladies Neuromusculaires Nantes/Angers, Service de Neurologie, Centre Hospitalier Universitaire d'Angers, France
- Neuromuscular Unit, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw
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Abstract
At present, more than 20 different forms of limb-girdle muscular dystrophies (LGMDs) are known (at least 7 autosomal dominant and 14 autosomal recessive). Although these different forms show some typical phenotypic characteristics, the existing clinical overlap makes their differential diagnosis difficult. Limb-girdle muscular dystrophy type 2 (LGMD2A) is the most prevalent LGMD in many European as well as Brazilian communities and is caused by mutations in the gene CAPN3. Laboratory testing, such as calpain immunohistochemistry and Western-blot analysis, is not totally reliable, since up to 20% of molecularly confirmed LGMD2A show normal content of calpain 3 and a third of LGMD2A biopsies have normal calpain 3 proteolytic activity in the muscle. Thus, genetic testing is considered as the only reliable diagnostic criterion in LGMD2A.
Material and methodsIn an attempt to find a correlation between genotype and muscle pathology in limb-girdle muscular dystrophy 2A we performed histopathological investigation of a group of 31 patients subdivided according to the type of pathologic CAPN3 gene mutation.
ResultsIn all biopsies typical features of muscular dystrophy such as fiber necrosis and regeneration, variation in fiber size and fibrosis were noted. Lobulated fibers were often encountered in the muscle biopsies of LGMD2A patients. Such fibers were more frequent in patients with 550delA mutation.
ConclusionsThese findings may be helpful in establishing diagnostic strategies in LGMD.
Abstract
At present, more than 20 different forms of limb-girdle muscular dystrophies (LGMDs) are known (at least 7 autosomal dominant and 14 autosomal recessive). Although these different forms show some typical phenotypic characteristics, the existing clinical overlap makes their differential diagnosis difficult. Limb-girdle muscular dystrophy type 2 (LGMD2A) is the most prevalent LGMD in many European as well as Brazilian communities and is caused by mutations in the gene CAPN3. Laboratory testing, such as calpain immunohistochemistry and Western-blot analysis, is not totally reliable, since up to 20% of molecularly confirmed LGMD2A show normal content of calpain 3 and a third of LGMD2A biopsies have normal calpain 3 proteolytic activity in the muscle. Thus, genetic testing is considered as the only reliable diagnostic criterion in LGMD2A.
Material and methodsIn an attempt to find a correlation between genotype and muscle pathology in limb-girdle muscular dystrophy 2A we performed histopathological investigation of a group of 31 patients subdivided according to the type of pathologic CAPN3 gene mutation.
ResultsIn all biopsies typical features of muscular dystrophy such as fiber necrosis and regeneration, variation in fiber size and fibrosis were noted. Lobulated fibers were often encountered in the muscle biopsies of LGMD2A patients. Such fibers were more frequent in patients with 550delA mutation.
ConclusionsThese findings may be helpful in establishing diagnostic strategies in LGMD.
Keywords
limb girdle muscular dystrophy, CAPN3, calpain, muscle biopsy
About this articleTitle
Muscle pathology in 31 patients with calpain 3 gene mutations
Journal
Neurologia i Neurochirurgia Polska
Issue
Pages
214-222
Page views
401
Article views/downloads
652
DOI
10.5114/ninp.2013.35490
Bibliographic record
Neurol Neurochir Pol 2013;47(3):214-222.
Keywords
limb girdle muscular dystrophy
CAPN3
calpain
muscle biopsy
Authors
Aleksandra A. Nadaj-Pakleza
Małgorzata Dorobek
Klaudia Nestorowicz
Barbara Ryniewicz
Elżbieta Szmidt-Sałkowska
Anna M. Kamińska
