title: Autosomal recessive limb-girdle muscular dystrophies in the Czech Republic.
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.
authors.forename: Kristýna
authors.initials: K
authors.lastname: Stehlíková
authors.forename: Daniela
authors.initials: D
authors.lastname: Skálová
authors.forename: Jana
authors.initials: J
authors.lastname: Zídková
authors.forename: Lenka
authors.initials: L
authors.lastname: Mrázová
authors.forename: Petr
authors.initials: P
authors.lastname: Vondráček
authors.forename: Radim
authors.initials: R
authors.lastname: Mazanec
authors.forename: Stanislav
authors.initials: S
authors.lastname: Voháňka
authors.forename: Jana
authors.initials: J
authors.lastname: Haberlová
authors.forename: Markéta
authors.initials: M
authors.lastname: Hermanová
authors.forename: Josef
authors.initials: J
authors.lastname: Zámečník
authors.forename: Ondřej
authors.initials: O
authors.lastname: Souček
authors.forename: Hana
authors.initials: H
authors.lastname: Ošlejšková
authors.forename: Nina
authors.initials: N
authors.lastname: Dvořáčková
authors.forename: Pavla
authors.initials: P
authors.lastname: Solařová
authors.affiliation: Centre of Molecular Biology and Gene Therapy, University Hospital Brno, Černopolní 9, Brno, 613 00, Czech Republic. lenka.fajkus@gmail.com.
authors.forename: Lenka
authors.initials: L
authors.lastname: Fajkusová
mesh_terms: D000075368:Anoctamins; D002154:Calpain / Q000235:genetics*; D018118:Chloride Channels / Q000235:genetics*; D018153:Czech Republic; D004252:DNA Mutational Analysis; D005838:Genotype; D006801:Humans; D009124:Muscle Proteins / Q000235:genetics*; D049288:Muscular Dystrophies, Limb-Girdle / Q000235:genetics*; D010430:Pentosyltransferases; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000235:genetics*; D049031:Sarcoglycans / Q000235:genetics*
chemical_list: C547813:ANO5 protein, human; D000075368:Anoctamins; D018118:Chloride Channels; D009124:Muscle Proteins; D011506:Proteins; C526571:SGCA protein, human; D049031:Sarcoglycans; C443107:FKRP protein, human; D010430:Pentosyltransferases; C105884:CAPN3 protein, human; D002154:Calpain