Inheritance patterns and phenotypic features of myofibrillar myopathy associated with a BAG3 mutation

• DOI: 10.1016/j.nmd.2010.05.004
• Publication Date: 2010-06-04T08:46:55Z
• Authors: Zagaa Odgerel; Anna Sarkozy; Hee-Suk Lee; Caoimhe McKenna; Julia Rankin; Volker Straub; Hanns Lochmüller; Francalanci Paola; Adele D’Amico; Enrico Bertini; Kate Bushby; Lev G. Goldfarb
• Keywords: Adult; Family Health; Male; Adolescent; Genotype; Proline; DNA Mutational Analysis; Actin Cytoskeleton; Young Adult; 03 medical and health sciences; Phenotype; 0302 clinical medicine; Muscular Diseases; Sural Nerve; Leucine; Mutation; Microscopy, Electron, Scanning; Humans; Female; Apoptosis Regulatory Proteins; Child; Adaptor Proteins, Signal Transducing

Myofibrillar myopathies are a heterogeneous group of neuromuscular disorders characterized by disintegration of myofibrils. The inheritance pattern is commonly autosomal dominant, but there has been a striking absence of secondary cases noted in a BAG3-associated subtype. We studied three families with BAG3 p.Pro209Leu mutation showing a severe phenotype of myofibrillar myopathy and axonal neuropathy with giant axons. In one family, transmission to a pair of siblings has occurred from their asymptomatic father who showed somatic mosaicism. In two other families, neither of the parents was affected or showed detectable level of somatic mosaicism. These observations suggest that the BAG3 variant of myofibrillar myopathy may result from a spontaneous mutation at an early point of embryonic development and that transmission from a mosaic parent may occur more than once. The study underlines the importance of parental evaluation as it may have implications for genetic counseling.