Two recurrent mutations are associated with GNE myopathy in the North of Britain.
OBJECTIVE
GNE myopathy is a rare recessive myopathy associated with inclusion bodies on muscle biopsy. The clinical phenotype is associated with distal muscle weakness with quadriceps sparing. Most of the current information on GNE myopathy has been obtained through studies of Jewish and Japanese patient cohorts carrying founder mutations in the GNE gene. However, little is known about GNE myopathy in Europe where the prevalence is thought to be very low.


METHODS
Patients were referred through the National Specialist Commissioning Team service for limb-girdle muscular dystrophies at Newcastle (UK). All patients harbouring mutations in the GNE gene were recruited for our study. Detailed clinical and genetic data as well as muscle MRIs and muscle biopsies were reviewed.


RESULTS
We identified 26 patients harbouring mutations in the GNE gene. Two previously reported mutations (c.1985C>T, p.Ala662Val and c.1225G>T, p.Asp409Tyr) were prevalent in the Scottish, Northern Irish and Northern English populations; with 90% of these patients carrying at least one of the two mutations. Clinically, we confirmed the homogenous pattern of selective quadriceps sparing but noted additional features like asymmetry of weakness at disease onset.


CONCLUSIONS
GNE myopathy is an important diagnosis to consider in patients presenting with distal leg muscle weakness. We report, for the first time, two common mutations in the north of Britain and highlight the broader spectrum of clinical phenotypes. We also propose that the prevalence of GNE myopathy may be underestimated due to the frequent absence of rimmed vacuoles in the muscle biopsy.
Institute of Genetic Medicine, MRC Centre for Neuromuscular Disease, Newcastle University, Newcastle upon Tyne, UK.
Amina
A
Chaouch
Institute of Genetic Medicine, MRC Centre for Neuromuscular Disease, Newcastle University, Newcastle upon Tyne, UK Institute of Neurological Sciences, Glasgow, UK.
Kathryn M
KM
Brennan
Institute of Genetic Medicine, MRC Centre for Neuromuscular Disease, Newcastle University, Newcastle upon Tyne, UK.
Judith
J
Hudson
West of Scotland Regional Genetics Service, Southern General Hospital, Glasgow, UK.
Cheryl
C
Longman
Belfast City Hospital, Belfast, UK.
John
J
McConville
Belfast City Hospital, Belfast, UK.
Patrick J
PJ
Morrison
Institute of Neurological Sciences, Glasgow, UK.
Maria E
ME
Farrugia
Institute of Neurological Sciences, Glasgow, UK.
Richard
R
Petty
Institute of Neurological Sciences, Glasgow, UK.
Willie
W
Stewart
Department of Neurology, King's College Hospital, London, UK.
Fiona
F
Norwood
Institute of Genetic Medicine, MRC Centre for Neuromuscular Disease, Newcastle University, Newcastle upon Tyne, UK.
Rita
R
Horvath
Institute of Genetic Medicine, MRC Centre for Neuromuscular Disease, Newcastle University, Newcastle upon Tyne, UK.
Patrick F
PF
Chinnery
National Institute for Neurology and Neurosurgery, Beaumont Hospital, Dublin, Ireland.
Donald
D
Costigan
Birmingham Muscle and Nerve Centre, Queen Elizabeth Hospital, Birmingham, UK.
John
J
Winer
Institute of Genetic Medicine, MRC Centre for Neuromuscular Disease, Newcastle University, Newcastle upon Tyne, UK.
Tuomo
T
Polvikoski
Institute of Pathology, Royal Victoria Hospital, Belfast, UK.
Estelle
E
Healy
Institute of Genetic Medicine, MRC Centre for Neuromuscular Disease, Newcastle University, Newcastle upon Tyne, UK.
Anna
A
Sarkozy
Institute of Genetic Medicine, MRC Centre for Neuromuscular Disease, Newcastle University, Newcastle upon Tyne, UK.
Teresinha
T
Evangelista
Institute of Genetic Medicine, MRC Centre for Neuromuscular Disease, Newcastle University, Newcastle upon Tyne, UK.
Oksana
O
Pogoryelova
Institute of Genetic Medicine, MRC Centre for Neuromuscular Disease, Newcastle University, Newcastle upon Tyne, UK.
Michelle
M
Eagle
Institute of Genetic Medicine, MRC Centre for Neuromuscular Disease, Newcastle University, Newcastle upon Tyne, UK.
Kate
K
Bushby
Institute of Genetic Medicine, MRC Centre for Neuromuscular Disease, Newcastle University, Newcastle upon Tyne, UK.
Volker
V
Straub
Institute of Genetic Medicine, MRC Centre for Neuromuscular Disease, Newcastle University, Newcastle upon Tyne, UK.
Hanns
H
Lochmüller
D000293:Adolescent; D000328:Adult; D002648:Child; D049310:Distal Myopathies / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009097:Multienzyme Complexes / Q000235:genetics*; D018908:Muscle Weakness / Q000235:genetics / Q000473:pathology; D018482:Muscle, Skeletal / Q000473:pathology; D009154:Mutation / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics; D006113:United Kingdom / Q000453:epidemiology; D055815:Young Adult
D009097:Multienzyme Complexes; C482901:UDP-N-acetylglucosamine 2-epimerase - N-acetylmannosamine kinase
GENETICS; INCL BODY MYOSITIS; MUSCLE DISEASE; MYOPATHY; NEUROMUSCULAR