title: Mutations in Czech LGMD2A patients revealed by analysis of calpain3 mRNA and their phenotypic outcome.
abstract: Calpain3 (CAPN3, p94) is a muscle-specific nonlysosomal cysteine proteinase. Loss of proteolytic function or change of other properties of this enzyme (such as stability or ability to interact with other muscular proteins) is manifested as limb girdle muscular dystrophy type 2A (LGMD2A, calpainopathy). These pathological changes in properties of calpain3 are caused by mutations in the calpain3 gene. The fact that the human gene for calpain3 is quite long led us to analyse its coding sequence by reverse transcription-PCR followed by sequence analysis. This study reports nine mutations that we found by analysing mRNA of seven unrelated LGMD patients in the Czech Republic. Three of these mutations were novel, not described on the Leiden muscular dystrophy pages so far. Further, we observed a reduction of dysferlin in muscle membrane in five of our seven LGMD2A patients by immunohistochemical analysis of muscle sections.
authors.affiliation: Center of Molecular Biology and Gene Therapy, University Hospital Brno, Cernopolni 9, CZ-62500 Brno, Czech Republic.
authors.forename: Tána
authors.initials: T
authors.lastname: Chrobáková
authors.forename: Markéta
authors.initials: M
authors.lastname: Hermanová
authors.forename: Iva
authors.initials: I
authors.lastname: Kroupová
authors.forename: Petr
authors.initials: P
authors.lastname: Vondrácek
authors.forename: Tat'ána
authors.initials: T
authors.lastname: Maríková
authors.forename: Radim
authors.initials: R
authors.lastname: Mazanec
authors.forename: Josef
authors.initials: J
authors.lastname: Zámecník
authors.forename: Jan
authors.initials: J
authors.lastname: Stanek
authors.forename: Miluse
authors.initials: M
authors.lastname: Havlová
authors.forename: Lenka
authors.initials: L
authors.lastname: Fajkusová
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001120:Arginine / Q000235:genetics; D015153:Blotting, Western / Q000379:methods; D002154:Calpain / Q000235:genetics* / Q000378:metabolism; D002648:Child; D018153:Czech Republic; D004252:DNA Mutational Analysis / Q000379:methods; D000073939:Dysferlin; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007527:Isoenzymes / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D049288:Muscular Dystrophies, Limb-Girdle / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014364:Tryptophan / Q000235:genetics
chemical_list: C114839:DYSF protein, human; D000073939:Dysferlin; D007527:Isoenzymes; D008565:Membrane Proteins; D009124:Muscle Proteins; D012333:RNA, Messenger; D014364:Tryptophan; D001120:Arginine; C105884:CAPN3 protein, human; D002154:Calpain