A case report: identification of a novel exon 1 deletion mutation in the GNE gene in a Chinese patient with GNE myopathy

Abstract

Rationale: GNE myopathy is caused by mutations in the UDP- N -acetylglucosamine-2-epimerase/ N -acetylmannosamine kinase( GNE ) gene and is clinically characterized by progressive weakness and atrophy of the lower-limb muscles with quadriceps sparing. Nearly all GNE mutations that have been reported thus far in various ethnic populations around the world have been missense or nonsense mutations. Patient concerns: We describe the case of a 32-year-old woman with GNE myopathy. The patient presented with progressive weakness of the lower-limb muscles that had spread to her legs. Her serum creatine kinase level was higher than the normal range. Mild myogenic changes were detected in the tibialis anterior muscles on electromyography, and moderate fatty infiltration was observed in various lower-limb muscles on magnetic resonance imaging. Histopathological examination of a skeletal muscle biopsy specimen revealed variation in muscle fiber size, rimmed vacuoles, and disorganized intermyofibrillar networks. DNA sequencing testing revealed a compound heterozygous mutation consisting of a known mutation (c.620A > T in exon 3) and a novel (exon 1 deletion) mutation. Diagnoses: Taken together, the clinical features, laboratory testing and DNA findings eventually made the diagnosis of GNE myopathy. Interventions and outcomes: Based on the diagnosis of the GNE myopathy, the patient was administered sialic acid 6 g a day for 1 year, and up to now, her symptoms did not progress further. Lessons: We have reported the case of a GNE myopathy patient with compound heterozygous GNE gene mutations. This case expands the genotypic spectrum of GNE myopathy.

The Role of Sialic Acid and Red Blood Cells Zeta Potential in Oxygen Transport from Bloodstream to Vital Organs and Tissues: Review of Current Data

“…У мышей с инактивированным геном данного фермента отмечается внутриутробная гибель плода, связанная с нарушением формирования микроциркуляторного русла головного мозга и внутрижелудочковым кровоизлиянием [45]. Дефект гена эпимеразы приводит к мышечной дистрофии у экспериментальных животных [46] и у человека [47,48]. Роль фермента в формировании гликокаликса эритроцитов не описана.…”

Pseudoexon activation by deep intronic variation in GNE myopathy with thrombocytopenia

“…5,6 In the past few decades, over 200 patients have been genetically confirmed in China as GNE myopathy with bi-allelic pathogenic variants. [7][8][9][10][11][12][13][14] However, some patients who appear to have GNE myopathy have been found to carry only one heterozygous pathogenic variant by sequencing exonic region of the GNE gene. It is to be expected that either large genomic rearrangements or variants affecting alternative splicing may largely contribute to the unresolved diagnosis.…”

“…Over 300 GNE variants associated with GNE myopathy have been reported, with missense pathogenic variants comprising the majority of the mutation spectrum (Human Gene Mutation Database Professional version 2023.1) 5,6 . In the past few decades, over 200 patients have been genetically confirmed in China as GNE myopathy with bi‐allelic pathogenic variants 7–14 . However, some patients who appear to have GNE myopathy have been found to carry only one heterozygous pathogenic variant by sequencing exonic region of the GNE gene.…”

GNE Myopathy and Duchenne Muscular Dystrophy in Two Moroccans Families

“…This enzyme catalyzes the first two successive steps in the biosynthesis of 5-N-acetylneuraminic acid (Neu5Ac), the common mammalian precursor of sialic acids (3). GNE myopathy worldwide prevalence is estimated at 1 to 9 per 1,000,000 (4). The first symptoms are most common in the third decade of life (5).…”

“…Muscles, Ligaments and Tendons Journal 2023;13(4) Najat SifeddiNe, Ghita amalou, majida Charif, et al…”