Dataset Information

Identification of a GNE homozygous mutation in a Han-Chinese family with GNE myopathy.

ABSTRACT: GNE myopathy is a rare, recessively inherited, early adult-onset myopathy, characterized by distal and proximal muscle degeneration which often spares the quadriceps. It is caused by mutations in the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase gene (GNE). This study aimed to identify the disease-causing mutation in a three-generation Han-Chinese family with members who have been diagnosed with myopathy. A homozygous missense mutation, c.1627G>A (p.V543M) in the GNE gene co-segregates with the myopathy present in this family. A GNE myopathy diagnosis is evidenced by characteristic clinical manifestations, rimmed vacuoles in muscle biopsies and the presence of biallelic GNE mutations. This finding broadens the GNE gene mutation spectrum and extends the GNE myopathy phenotype spectrum.

SUBMITTER: Wu Y

PROVIDER: S-EPMC6201217 | biostudies-other | 2018 Nov

REPOSITORIES: biostudies-other

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Identification of a GNE homozygous mutation in a Han-Chinese family with GNE myopathy.

Wu Yuan Y Yuan Lamei L Guo Yi Y Lu Anjie A Zheng Wen W Xu Hongbo H Yang Yan Y Hu Pengzhi P Gu Shaojuan S Wang Bingqi B Deng Hao H

Journal of cellular and molecular medicine 20180829 11

GNE myopathy is a rare, recessively inherited, early adult-onset myopathy, characterized by distal and proximal muscle degeneration which often spares the quadriceps. It is caused by mutations in the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase gene (GNE). This study aimed to identify the disease-causing mutation in a three-generation Han-Chinese family with members who have been diagnosed with myopathy. A homozygous missense mutation, c.1627G>A (p.V543M) in the GNE gene co-seg ...[more]

PMID: 30160005

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Project description:GNE myopathy is a rare genetic disease characterized by progressive muscle atrophy and weakness. It is caused by biallelic mutations in the GNE gene that encodes for the bifunctional enzyme, uridine diphosphate (UDP)-N-acetylglucosamine (GlcNAc) 2-epimerase/N-acetylmannosamine (ManNAc) kinase. Typical characteristics of GNE myopathy include progressive myopathy, first involving anterior tibialis muscle and sparing the quadriceps, and rimmed vacuoles on muscle biopsy. Identifying biallelic mutations by sequencing of the GNE gene confirms the diagnosis of GNE myopathy. In a subset of patients, diagnostic confirmation is challenged by the identification of mutations in only one allele, suggesting mutations in deep intronic regions or regulatory regions.We performed targeted sequencing and copy number variant (CNV) analysis of GNE in two siblings who clinically presented with GNE myopathy. Further molecular and biochemical studies were done to characterize the effect of a previously uncharacterized GNE mutation.We report two siblings of Indian descent with characteristic features of GNE myopathy, including progressive skeletal muscle weakness initially involving the anterior tibialis, and rimmed vacuoles on muscle biopsy, in which a heterozygous mutation, p.Val727Met, was identified in both affected siblings, but no other deleterious variants in either coding region or exon-intron boundaries of the gene. Subsequent insertion/deletion analysis identified a novel 11.3-kb deletion (Chr9 [GRCh37]: g.36257583_36268910del) encompassing the GNE promoter region, with breakpoints residing in Alu repeats. Gene expression analysis revealed reduced GNE mRNA and protein levels, confirming decreased expression of the deleted allele harboring the deletion.We have identified GNE as one of the genes susceptible to Alu-mediated recombination. Our findings suggest that the deletion may encompass the promoter or another region necessary for GNE expression. In patients with typical manifestations of GNE myopathy and a single GNE variant identified, copy number variant (CNV) analysis may be useful in arriving at the diagnosis.

Dataset Information

Identification of a GNE homozygous mutation in a Han-Chinese family with GNE myopathy.

Publications

Identification of a GNE homozygous mutation in a Han-Chinese family with GNE myopathy.

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