Clinical Characteristics and Molecular Genetic Analysis of Korean Patients with GNE Myopathy

Abstract

PurposeGlucosamine (UDP-N-acetyl)-2-epimerase/N-acetylmannosamine kinase (GNE) myopathy is an autosomal recessive neuromuscular disorder characterized by early adult-onset weakness of the distal muscles of the lower limbs. The clinical spectrum of GNE myopathy varies, and it is not clear how the same GNE gene mutations can result in different phenotypes. Here, we present clinical, pathological and genetic characteristics of twenty-one Korean patients with GNE myopathy.Materials and MethodsTwenty-one GNE myopathy patients were included in this study, conducted from 2004 to 2011. Based on medical records, patients' gender, onset age, family history, clinical history, serum creatine kinase (CK) level, neurologic examination, findings of muscle biopsy, muscle imaging findings and electrophysiologic features were extensively reviewed. Mutation of the GNE gene (9p13.3) was confirmed by DNA direct sequencing analysis in all patients.ResultsThe mean onset age was 23.8±8.8 years (mean±SD). Patient serum CK levels were slightly to moderately elevated, ranging from 41 to 2610 IU. Among the patients, twelve patients were female and nine patients were male. Except for eight patients, all of the patients presented initially with only distal muscle weakness in the lower extremities. The most common mutation was V572L, followed by C13S.ConclusionThe clinical manifestations of our patients with GNE mutations varied. Among twenty-one patients, thirteen patients showed the typical GNE myopathy phenotype. There was no relationship between clinical features and site of mutation. Therefore, we suggest that neither homozygous nor compound heterozygous models are correlated with disease phenotype or disease severity.

Clinical and Electrophysiological Findings in Hereditary Inclusion Body Myopathy Compared With Sporadic Inclusion Body Myositis

“…18 Earlier electrophysiological reports of GNE-hIBM included a large case series of 21 Korean patients, most with purely myopathic and only 3 with mixed neurogenic/myopathic MUPs. 26 Pure myopathic changes sparing the quadriceps were also described. 19,21,23 Neurogenic MUPs were reported in 2 additional GNEhIBM cases.…”

“…13 Reported description of the electromyographic (EMG) findings in genetically proven hIBM patients show some resemblance to those encountered in sIBM with essentially mixed myopathic and neurogenic features. 9,[13][14][15][16][17][18][19][20][21][22][23][24][25][26] In this study, we describe the clinical and electrophysiological features of hIBM subjects in comparison with their sIBM counterparts to identify differences that might help the clinical differential diagnosis.…”

Distal Myopathy with Rimmed Vacuoles Confirmed by Whole Exome Sequencing

“…However, the diagnosis of DMRV is not always easy. Expansion of mutational analysis in GNE gene has indicated that DMRV patients often have an atypical clinical presentation that includes proximal muscle weakness [16,26]. Muscle biopsy is necessary for histopathological evaluation, but is a very invasive method.…”

Genetics of GNE myopathy in the non-Jewish Persian population

“…The mean onset age for these patients were 23.2 (p.V603L) and 30 (p.C44S) years. 33 Cardiac involvement has been reported in a number of GNE myopathy patients, with a higher prevalence (18%) in Japanese patients. 28 Moreover, a recent animal study revealed the important role of GNE in the early development of cardiac muscles.…”