A Novel Mutation in a Large French-Canadian Family with LGMD1B

Nicolas Chrestian, Paul N. Valdmanis, Najmeddine Echahidi, Denis Brunet, Jean-Pierre Bouchard, Peter Gould, Guy A. Rouleau, Jean Champagne, Nicolas Dupré
2008 Canadian Journal of Neurological Sciences  
ABSTRACTBackground: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 theLMNAgene causing limb girdle muscular dystrophy type 1B.Methods:We identified a large French Canadian family with the LGMD 1B phenotype and a cardiac
more » ... disease phenotype that carried a new mutation in theLMNAgene 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)LMNAgene 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 theLMNAgene in a French-Canadian family. This diagnosis has important implications for affected patients and their siblings since they may eventually require pacemaker implantation.
doi:10.1017/s031716710000891x fatcat:ptxez2z735asbdsxusa6f7jm3i