Lookup NU author(s): Dr Oksana Pogoryelova,
Professor Hanns Lochmuller
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2017 The Authors. GNE myopathy is a rare distal myopathy, caused by mutations in the GNE gene, affecting sialic acid synthesis. Clinical presentation varies from asymptomatic early stage patients to severely debilitating forms. This first report describes clinical presentations and severity of the disease, using data of 150 patients collected via the on-line, patient-reported registry component of the GNE Myopathy Disease Monitoring Program (GNEM-DMP). Disease progression was prospectively analysed, over a 2-year period, using the GNE myopathy functional activity scale (GNEM-FAS). The average annual rates of decline in function were estimated at -9.6% and -3.2% in ambulant and non-ambulant patients respectively. 4.3% of participants became non-ambulant within one year. The mean time from onset to required use of a wheelchair was 11.9 years. Mean delay of genetic diagnosis from symptom onset was 5.2 years. Mutation specific analysis demonstrated genotype-phenotype relationships; i.e. p.Ala662Val may be associated with a more severe phenotype, compared to p.Val727Met. Patients with compound heterozygous mutation in epimerase and kinase domain appeared to have a more severe phenotype compared to patients with both mutations located within one domain. Acknowledging the limitations of the study, these findings suggest that the severity of the GNE mutations affects disease severity. The GNEM-DMP is a useful data collection tool, prospectively measuring the progression of GNE myopathy, which could play an important role in translational and clinical research and further understanding of genotype-phenotype correlations.
Author(s): Pogoryelova O, Cammish P, Mansbach H, Argov Z, Nishino I, Skrinar A, Chan Y, Nafissi S, Shamshiri H, Kakkis E, Lochmuller H
Publication type: Article
Publication status: Published
Journal: Neuromuscular Disorders
Print publication date: 01/02/2018
Online publication date: 14/11/2017
Acceptance date: 06/11/2017
ISSN (print): 0960-8966
ISSN (electronic): 1873-2364
Publisher: Elsevier Ltd
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