Open Access Research article

Autosomal recessive limb-girdle muscular dystrophies in the Czech Republic

Kristýna Stehlíková12, Daniela Skálová12, Jana Zídková12, Lenka Mrázová3, Petr Vondráček3, Radim Mazanec4, Stanislav Voháňka5, Jana Haberlová6, Markéta Hermanová7, Josef Zámečník8, Ondřej Souček9, Hana Ošlejšková3, Nina Dvořáčková10, Pavla Solařová11 and Lenka Fajkusová12*

Author Affiliations

1 Centre of Molecular Biology and Gene Therapy, University Hospital Brno, Černopolní 9, Brno, 613 00, Czech Republic

2 Central European Institute of Technology, Masaryk University, Kamenice 5, Brno, CZ-62500, Czech Republic

3 Department of Child Neurology, University Hospital Brno, Černopolní 9, Brno, 613 00, Czech Republic

4 Department of Neurology, Second Faculty of Medicine, Charles University and University Hospital Motol, V Úvalu 84, Prague, 150 06, Czech Republic

5 Department of Neurology, University Hospital Brno, Jihlavská 20, Brno, 625 00, Czech Republic

6 Department of Child Neurology, Second Faculty of Medicine, Charles University and University Hospital Motol, V Úvalu 84, Prague, 150 06, Czech Republic

7 First Department of Pathological Anatomy, Faculty of Medicine, Masaryk University and St. Anne’s University Hospital, Pekařská 53, Brno, 656 91, Czech Republic

8 Department of Pathology and Molecular Medicine, Second Faculty of Medicine, Charles University and University Hospital Motol, V Úvala 84, Prague, 150 06, Czech Republic

9 Institute of Pathology, University Hospital Brno, Jihlavská 20, Brno, 625 00, Czech Republic

10 Departmemt of Medical Genetics, University Hospital Ostrava, 17. Listopadu 1790, Ostrava, 708 52, Czech Republic

11 Department of Medical Genetics, University Hospital Hradec Králové, Sokolská 581, 500 05 Hradec Králové, Ostrava, Czech Republic

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BMC Neurology 2014, 14:154  doi:10.1186/s12883-014-0154-7

Published: 19 August 2014

Abstract

Background

Autosomal recessive limb-girdle muscular dystrophies (LGMD2) include a number of disorders with heterogeneous etiology that cause predominantly weakness and wasting of the shoulder and pelvic girdle muscles. In this study, we determined the frequency of LGMD subtypes within a cohort of Czech LGMD2 patients using mutational analysis of the CAPN3, FKRP, SGCA, and ANO5 genes.

Methods

PCR-sequencing analysis; sequence capture and targeted resequencing.

Results

Mutations of the CAPN3 gene are the most common cause of LGMD2, and mutations in this gene were identified in 71 patients in a set of 218 Czech probands with a suspicion of LGMD2. Totally, we detected 37 different mutations of which 12 have been described only in Czech LGMD2A patients. The mutation c.550delA is the most frequent among our LGMD2A probands and was detected in 47.1% of CAPN3 mutant alleles. The frequency of particular forms of LGMD2 was 32.6% for LGMD2A (71 probands), 4.1% for LGMD2I (9 probands), 2.8% for LGMD2D (6 probands), and 1.4% for LGMD2L (3 probands).

Further, we present the first results of a new approach established in the Czech Republic for diagnosis of neuromuscular diseases: sequence capture and targeted resequencing. Using this approach, we identified patients with mutations in the DYSF and SGCB genes.

Conclusions

We characterised a cohort of Czech LGMD2 patients on the basis of mutation analysis of genes associated with the most common forms of LGMD2 in the European population and subsequently compared the occurrence of particular forms of LGMD2 among countries on the basis of our results and published studies.

Keywords:
Calpain-3; CAPN3; Limb girdle muscular dystrophy; LGMD2; Sequence capture