title: A novel mutation in a large French-Canadian family with LGMD1B.
abstract: BACKGROUND
  Limb girdle muscular dystrophy type 1B is an autosomal dominant disease characterized by late onset proximal muscle involvement associated with cardiac complications such as atrioventricular conduction blocks, dilated cardiomyopathy, and sudden death.
  
  
  OBJECTIVE
  Define the full phenotypic spectrum of a new mutation in the LMNA gene causing limb girdle muscular dystrophy type 1B.
  
  
  METHODS
  We identified a large French Canadian family with the LGMD 1B phenotype and a cardiac conduction disease phenotype that carried a new mutation in the LMNA gene and sought to define its full phenotypic spectrum by performing complete neurological and cardiac evaluations, muscle biopsy, RNA and DNA studies.
  
  
  RESULTS
  The proband and 12 living at risk relatives were tested. In total, we identified seven carriers of a new (IVS9-3C > G) LMNA gene mutation. Of the three symptomatic patients, all had cardiac involvement, but only two presented proximal limb weakness. The one available muscle biopsy demonstrated a normally expressed lamin A/C protein, localized at the nuclear envelope. RNA study revealed a loss of exon 10 transcription caused by the IVS9-3C to G splicing mutation.
  
  
  CONCLUSIONS
  We have identified a new mutations in the LMNA gene in a French-Canadian family. This diagnosis has important implications for affected patients and their siblings since they may eventually require pacemaker implantation.
authors: Faculty of Medicine, Laval University, Quebec City, Canada.
authors: Nicolas
authors: N
authors: Chrestian
authors: Paul N
authors: PN
authors: Valdmanis
authors: Najmeddine
authors: N
authors: Echahidi
authors: Denis
authors: D
authors: Brunet
authors: Jean-Pierre
authors: JP
authors: Bouchard
authors: Peter
authors: P
authors: Gould
authors: Guy A
authors: GA
authors: Rouleau
authors: Jean
authors: J
authors: Champagne
authors: Nicolas
authors: N
authors: Dupré
mesh_terms: D000328:Adult; D000368:Aged; D017398:Alternative Splicing; D019943:Amino Acid Substitution; D054537:Atrioventricular Block / Q000150:complications / Q000235:genetics*; D016022:Case-Control Studies; D004247:DNA / Q000032:analysis; D005260:Female; D006801:Humans; D034904:Lamin Type A / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D049288:Muscular Dystrophies, Limb-Girdle / Q000150:complications / Q000235:genetics*; D010375:Pedigree; D012313:RNA / Q000032:analysis; D012016:Reference Values
chemical_list: C494847:LMNA protein, human; D034904:Lamin Type A; D012313:RNA; D004247:DNA