TY - JOUR
T1 - BAG3 mutations
T2 - Another cause of giant axonal neuropathy
AU - Jaffer, Fatima
AU - Murphy, Sinéad M.
AU - Scoto, Mariacristina
AU - Healy, Estelle
AU - Rossor, Alexander M.
AU - Brandner, Sebastian
AU - Phadke, Rahul
AU - Selcen, Duygu
AU - Jungbluth, Heinz
AU - Muntoni, Francesco
AU - Reilly, Mary M.
N1 - Copyright:
Copyright 2012 Elsevier B.V., All rights reserved.
PY - 2012/6
Y1 - 2012/6
N2 - 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 ofBAG3-associated myofibrillarmyopathy 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.
AB - 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 ofBAG3-associated myofibrillarmyopathy 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.
KW - BAG3
KW - Bcl-2 associated athanogene
KW - Charcot-Marie-Tooth disease
KW - Giant axons
KW - Myofibrillar myopathy
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U2 - 10.1111/j.1529-8027.2012.00409.x
DO - 10.1111/j.1529-8027.2012.00409.x
M3 - Article
C2 - 22734908
AN - SCOPUS:84863441874
SN - 1085-9489
VL - 17
SP - 210
EP - 216
JO - Journal of the Peripheral Nervous System
JF - Journal of the Peripheral Nervous System
IS - 2
ER -