Inheritance patterns and phenotypic features of myofibrillar myopathy associated with a BAG3 mutation.
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.
Odgerel
Zagaa
Z
National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-9404, USA.
Sarkozy
Anna
A
Lee
Hee-Suk
HS
McKenna
Caoimhe
C
Rankin
Julia
J
Straub
Volker
V
Lochmüller
Hanns
H
Paola
Francalanci
F
D'Amico
Adele
A
Bertini
Enrico
E
Bushby
Kate
K
Goldfarb
Lev G
LG
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
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C414431:BAG3 protein, human; D011392:Proline; D007930:Leucine