[Distal myopathy due to mutations of GNE gene: clinical spectrum and diagnosis].
Distal myopathies are rare muscular disorders clinically characterized by a predominantly distal muscular involvement. Among recessive forms, the myopathy resulting from mutations in the UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase (GNE) gene, often designated as Nonaka myopathy, primarily affect young adults and are characterized by muscle wasting and weakness predominating on the anterior compartment of the leg, a remarkable quadriceps sparing and a frequent evolution towards ambulation loss after a few years. Finding rimmed vacuoles on muscle biopsy is a further argument for the diagnosis. However, the presentation and course may vary and we describe four patients who illustrate the clinical spectrum of the disease: the first patient had a classical form with progressive weakness over several years, the second one a rapidly progressive myopathy leading to ambulation loss within three years from onset, the third one a very slow course with no ambulation loss after several decades, and the last one a progressive form with misleading neurogenic features on the EMG. One of our four patients harbored a homozygous mutation, and three others were compound heterozygous, two of them displaying an original mutation: one had a c.2036 T>G (p.Val679Gly) substitution, the c.829 C>T (p.Arg277Cys) substitution.
Béhin
A
A
Centre de référence des maladies rares neuromusculaires, institut de myologie, groupe hospitalier Pitié-Salpêtrière, AP-HP, 47-83, boulevard de l'Hôpital, Paris, France. anthony.behin@psl.aphp.fr
Dubourg
O
O
Laforêt
P
P
Pêcheux
C
C
Bernard
R
R
Lévy
N
N
Eymard
B
B
D000273:Adipose Tissue / Q000473:pathology; D000328:Adult; D000368:Aged; D049310:Distal Myopathies / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D004576:Electromyography; D005260:Female; D006801:Humans; D007866:Leg / Q000473:pathology; D008297:Male; D008875:Middle Aged; D018485:Muscle Fibers, Skeletal / Q000473:pathology; D018482:Muscle, Skeletal / Q000473:pathology; D009154:Mutation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics*; D013710:Tendons / Q000473:pathology; D014057:Tomography, X-Ray Computed; D019282:Wasting Syndrome / Q000473:pathology
D017853:Phosphotransferases (Alcohol Group Acceptor); C018765:N-acylmannosamine kinase