Clinical and molecular genetic analysis in Chinese patients with distal myopathy with rimmed vacuoles

Li, Honghao; Chen, Qi; Liu, Fuchen; Zhang, Xuemei; Liu, Tao; Li, Wei; Liu, Shuping; Zhao, Yuying; Wen, Bing; Dai, Tao; Lin, Pengfei; Gong, Yaoqin; Yan, Chuanzhu

doi:10.1038/jhg.2011.15

Cited by 20 publications

(17 citation statements)

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“…The quadriceps muscles were involved in only one (25%) of our patients (9a, Table 1) with this variant; however, still with less severity than other thigh and pelvic girdle muscles, whereas three of nine previously reported patients had affected quadriceps. One of the previous cases 48 (Taiwanese-1, Table 1) had an incomplete right bundle branch block, but none of our or other previously reported patients had any cardiac abnormality. The involvement of upper limbs was more marked in the Taiwanese patients than that of the others.…”

Section: Phenotype Spectrum Of Variantscontrasting

confidence: 40%

Genetics of GNE myopathy in the non-Jewish Persian population

et al. 2015

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Section: Phenotype Spectrum Of Variantscontrasting

confidence: 40%

Genetics of GNE myopathy in the non-Jewish Persian population

et al. 2015

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“…Since the V572L mutation was also shown to be the most frequent mutation in Koreans,13 a common founder effect might exist between these populations. The most common mutation in China is L508S,15 and V696M in Thailand 16…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2013

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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.

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“…All GNE myopathy patients were clinically and genetically diagnosed Mongoloid individuals who visited the Peripheral Neuropathy and Myopathy Department of Qilu Hospital (Table S1). The method of GNE gene sequencing was performed as described earlier and partial results (patient 1–6) have been reported [13]. The control muscle specimens were collected from individuals who had undergone muscle biopsy and were eventually diagnosed as normal.…”

Section: Methodsmentioning

confidence: 99%

Unfolded Protein Response and Activated Degradative Pathways Regulation in GNE Myopathy

Chen

Liu

et al. 2013

PLoS ONE

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Although intracellular beta amyloid (Aβ) accumulation is known as an early upstream event in the degenerative course of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) myopathy, the process by which Aβdeposits initiate various degradative pathways, and their relationship have not been fully clarified. We studied the possible secondary responses after amyloid beta precursor protein (AβPP) deposition including unfolded protein response (UPR), ubiquitin proteasome system (UPS) activation and its correlation with autophagy system. Eight GNE myopathy patients and five individuals with normal muscle morphology were included in this study. We performed immunofluorescence and immunoblotting to investigate the expression of AβPP, phosphorylated tau (p-tau) and endoplasmic reticulum molecular chaperones. Proteasome activities were measured by cleavage of fluorogenic substrates. The expression of proteasome subunits and linkers between proteasomal and autophagy systems were also evaluated by immunoblotting and relative quantitative real-time RT-PCR. Four molecular chaperones, glucose-regulated protein 94 (GRP94), glucose-regulated protein 78 (GRP78), calreticulin and calnexin and valosin containing protein (VCP) were highly expressed in GNE myopathy. 20S proteasome subunits, three main proteasome proteolytic activities, and the factors linking UPS and autophagy system were also increased. Our study suggests that AβPP deposition results in endoplasmic reticulum stress (ERS) and highly expressed VCP deliver unfolded proteins from endoplasmic reticulum to proteosomal system which is activated in endoplasmic reticulum associated degradation (ERAD) in GNE myopathy. Excessive ubiquitinated unfolded proteins are exported by proteins that connect UPS and autophagy to autophagy system, which is activated as an alternative pathway for degradation.

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Clinical and molecular genetic analysis in Chinese patients with distal myopathy with rimmed vacuoles

Cited by 20 publications

References 18 publications

Genetics of GNE myopathy in the non-Jewish Persian population

Genetics of GNE myopathy in the non-Jewish Persian population

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

Unfolded Protein Response and Activated Degradative Pathways Regulation in GNE Myopathy

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