BAG3 mutations: another cause of giant axonal neuropathy.
Mutations in Bcl-2 associated athanogene-3 (BAG3) are a rare cause of myofibrillar myopathy, characterised by rapidly progressive proximal and axial myopathy, cardiomyopathy and respiratory compromise. Neuropathy has been documented neurophysiologically in previously reported cases of BAG3-associated myofibrillar myopathy and in some cases giant axons were observed on nerve biopsies; however, neuropathy was not thought to be a dominant feature of the disease. In the context of inherited neuropathy, giant axons are typically associated with autosomal recessive giant axonal neuropathy caused by gigaxonin mutations but have also been reported in association with NEFL- and SH3TC2-associated Charcot-Marie-Tooth disease. Here, we describe four patients with heterozygous BAG3 mutations with clinical evidence of a sensorimotor neuropathy, with predominantly axonal features on neurophysiology. Three patients presented with a significant neuropathy. Muscle magnetic resonance imaging (MRI) in one patient revealed mild to moderate atrophy without prominent selectivity. Examination of sural nerve biopsies in two patients demonstrated giant axons. This report confirms the association of giant axonal neuropathy with BAG3-associated myofibrillar myopathy, and highlights that neuropathy may be a significant feature.
MRC Centre for Neuromuscular Diseases, Department of Molecular Neurosciences, UCL Institute of Neurology and The National Hospital for Neurology and Neurosurgery, London, UK.
Fatima
F
Jaffer
Sinéad M
SM
Murphy
Mariacristina
M
Scoto
Estelle
E
Healy
Alexander M
AM
Rossor
Sebastian
S
Brandner
Rahul
R
Phadke
Duygu
D
Selcen
Heinz
H
Jungbluth
Francesco
F
Muntoni
Mary M
MM
Reilly
D000200:Action Potentials / Q000502:physiology; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000293:Adolescent; D051017:Apoptosis Regulatory Proteins; D002648:Child; D004576:Electromyography; D005260:Female; D056768:Giant Axonal Neuropathy / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D009154:Mutation
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C414431:BAG3 protein, human