title: Inheritance patterns and phenotypic features of myofibrillar myopathy associated with a BAG3 mutation.
abstract: 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.
authors.affiliation: National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-9404, USA.
authors.forename: Zagaa
authors.initials: Z
authors.lastname: Odgerel
authors.forename: Anna
authors.initials: A
authors.lastname: Sarkozy
authors.forename: Hee-Suk
authors.initials: HS
authors.lastname: Lee
authors.forename: Caoimhe
authors.initials: C
authors.lastname: McKenna
authors.forename: Julia
authors.initials: J
authors.lastname: Rankin
authors.forename: Volker
authors.initials: V
authors.lastname: Straub
authors.forename: Hanns
authors.initials: H
authors.lastname: Lochmüller
authors.forename: Francalanci
authors.initials: F
authors.lastname: Paola
authors.forename: Adele
authors.initials: A
authors.lastname: D'Amico
authors.forename: Enrico
authors.initials: E
authors.lastname: Bertini
authors.forename: Kate
authors.initials: K
authors.lastname: Bushby
authors.forename: Lev G
authors.initials: LG
authors.lastname: Goldfarb
mesh_terms: D008841:Actin Cytoskeleton / Q000473:pathology* / Q000648:ultrastructure; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D051017:Apoptosis Regulatory Proteins; D002648:Child; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D005838:Genotype; D006801:Humans; D007930:Leucine / Q000235:genetics; D008297:Male; D008855:Microscopy, Electron, Scanning; D009135:Muscular Diseases / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D011392:Proline / Q000235:genetics; D013497:Sural Nerve / Q000473:pathology / Q000648:ultrastructure; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C414431:BAG3 protein, human; D011392:Proline; D007930:Leucine