We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Recessive GNE Mutations in Korean Nonaka Distal Myopathy Patients with or without Peripheral Neuropathy.
- Authors
Tamanna, Nasrin; Pi, Byung Kwon; Lee, Ah Jin; Kanwal, Sumaira; Choi, Byung-Ok; Chung, Ki Wha
- Abstract
Autosomal recessive Nonaka distal myopathy is a rare autosomal recessive genetic disease characterized by progressive degeneration of the distal muscles, causing muscle weakness and decreased grip strength. It is primarily associated with mutations in the GNE gene, which encodes a key enzyme of sialic acid biosynthesis (UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase). This study was performed to find GNE mutations in six independent distal myopathy patients with or without peripheral neuropathy using whole-exome sequencing (WES). In silico pathogenic prediction and simulation of 3D structural changes were performed for the mutant GNE proteins. As a result, we identified five pathogenic or likely pathogenic missense variants: c.86T>C (p.Met29Thr), c.527A>T (p.Asp176Val), c.782T>C (p.Met261Thr), c.1714G>C (p.Val572Leu), and c.1771G>A (p.Ala591Thr). Five affected individuals showed compound heterozygous mutations, while only one patient revealed a homozygous mutation. Two patients revealed unreported combinations of combined heterozygous mutations. We observed some specific clinical features, such as complex phenotypes of distal myopathy with distal hereditary peripheral neuropathy, an earlier onset of weakness in legs than that of hands, and clinical heterogeneity between two patients with the same set of compound heterozygous mutations. Our findings on these genetic causes expand the clinical spectrum associated with the GNE mutations and can help prepare therapeutic strategies.
- Subjects
PERIPHERAL neuropathy; FAMILIAL spastic paraplegia; NEMALINE myopathy; MUSCLE diseases; MUSCLE weakness; GENETIC mutation; GRIP strength
- Publication
Genes, 2024, Vol 15, Issue 4, p485
- ISSN
2073-4425
- Publication type
Article
- DOI
10.3390/genes15040485