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GNE myopathy is caused by mutations in the gene encoding glucosamine (UDP-N-acetyl)-2-epime-rase/N-acetylmannosamine kinase (GNE).However,the mechanisms through which point mutations in the GNE gene can lead to GNE myopathy remain unclear.We reported a novel pathogenic point mutation in the GNE gene and investigated the pathogenic effects of codon 511 (p.P511 S) in this family and p.P511H reported in early liter-ature on GNE myopathy.Clinical manifestations and examinations of the proband were consistent with the diagnosis of GNE myopathy.A novel point mutation in the GNE gene on exon 9 (c.1624C > T,Pro511Ser) was identified in the family.Predictions with Mutation Taster and SIFT indicated pathogenicity of both the p.P511S variant and the p.P511H variant.Crystal structure models built by Modeller showed similar overall secondary and tertiary struc-tures of wild-type and variants.But the variants exhibited decreased stability and rigid flexibility,resulting from in-creased free energy and altered local solvent accessibility.These mutations were expected to affect the catalytic ac-tivity of the enzyme,leading to GNE myopathy.These findings expand the genetic spectrum of mutations causing GNE myopathy in China and explain the probable molecular mechanisms of GNE myopathy resulting from point mu-tations in the GNE gene.