Clinical features, lectin staining, and a novel GNE frameshift mutation in hereditary inclusion body myopathy.
We present a comprehensive report of two siblings with hereditary inclusion body myopathy (HIBM). The clinical features and histological characteristics of the muscle biopsies showed the typical pattern of predominantly distal vacuolar myopathy with quadriceps sparing. This was confirmed by muscle MRI. PNA lectin staining showed an increased signal at the sarcolemma in patient muscle sections compared to control muscle, indicating reduced sialylation of glycoconjugates. Mutation analysis revealed compound heterozygous mutations in the GNE gene, encoding the key enzyme in sialic acid synthesis UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase: a missense mutation (c.2086G > A; p.V696M) previously described in HIBM patients of Indian origin, and a novel frame shift mutation (c.1295delA; p.K432RfsX17) leading to a premature stopcodon. These findings confirmed the diagnosis of HIBM on the histological, molecular and biochemical level.
Voermans
N C
NC
Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands. n.voermans@neuro.umcn.nl
Guillard
M
M
Doedée
R
R
Lammens
M
M
Huizing
M
M
Padberg
G W
GW
Wevers
R A
RA
van Engelen
B G
BG
Lefeber
D J
DJ
D000328:Adult; D004252:DNA Mutational Analysis; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D007525:Isoelectric Focusing; D008279:Magnetic Resonance Imaging; D008297:Male; D009097:Multienzyme Complexes / Q000235:genetics*; D018482:Muscle, Skeletal / Q000201:enzymology / Q000473:pathology; D018979:Myositis, Inclusion Body / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D009439:Neuraminidase; D019887:Peanut Agglutinin; D016133:Polymerase Chain Reaction; D035781:Siblings
D009097:Multienzyme Complexes; D019887:Peanut Agglutinin; C482901:UDP-N-acetylglucosamine 2-epimerase - N-acetylmannosamine kinase; D009439:Neuraminidase