open access

Vol 47, No 3 (2013)
ARTYKUŁ ORYGINALNY
Submitted: 2011-12-21
Get Citation

Muscle pathology in 31 patients with calpain 3 gene mutations

Aleksandra A. Nadaj-Pakleza, Małgorzata Dorobek, Klaudia Nestorowicz, Barbara Ryniewicz, Elżbieta Szmidt-Sałkowska, Anna M. Kamińska
DOI: 10.5114/ninp.2013.35490
·
Neurol Neurochir Pol 2013;47(3):214-222.

open access

Vol 47, No 3 (2013)
ARTYKUŁ ORYGINALNY
Submitted: 2011-12-21

Abstract

Background and purpose

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 methods

In 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.

Results

In 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.

Conclusions

These findings may be helpful in establishing diagnostic strategies in LGMD.

Abstract

Background and purpose

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 methods

In 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.

Results

In 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.

Conclusions

These findings may be helpful in establishing diagnostic strategies in LGMD.

Get Citation

Keywords

limb girdle muscular dystrophy, CAPN3, calpain, muscle biopsy

About this article
Title

Muscle pathology in 31 patients with calpain 3 gene mutations

Journal

Neurologia i Neurochirurgia Polska

Issue

Vol 47, No 3 (2013)

Pages

214-222

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

Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

By "Via Medica sp. z o.o." sp.k., ul. Świętokrzyska 73, 80–180 Gdańsk, Poland
tel.:+48 58 320 94 94, fax:+48 58 320 94 60, e-mail: viamedica@viamedica.pl