Mutational spectrum and clinical features in 35 unrelated mainland Chinese patients with GNE myopathy

• The mutational spectrum and clinical profiles of 35 Chinese patients with GNE myopathy are reported.
• 16 novel and 13 previously reported GNE mutations were identified.
• The p.D176V mutation was the most common mutation in this group of patients.
• There is phenotypic heterogeneity among patients with GNE myopathy.
• Muscle magnetic resonance imaging can be useful for differential diagnosis.

GNE myopathy is an autosomal recessive distal myopathy caused by biallelic mutation in the GNE gene. It shows great genetic heterogeneity among different ethnic groups. In this study, we summarized the mutational spectrum and clinical profiles in 35 unrelated GNE myopathy patients from mainland China. Molecular analysis revealed 16 novel (p.G47D, p.F66Y, p.E173A, p.Y186H, p.R246L, p.R263*, p.R306*, p.A366D, p.V512M, p.C520Y, p.G545R, p.G548S, p.V622G, p.A638P, IVS2 + 1G > A and c.2112delC) and 13 reported mutations. Notably, the p.D176V mutation was detected in 65.7% (23/35) of this patient cohort, giving an allele frequency of 34.3% (24/70). We estimated the carrier frequency of p.D176V to be 0.19% (1/520) in the normal population, although haplotype analysis indicated no founder effect in the patients carrying p.D176V mutation. Clinically, 29 patients presented with the classic phenotype of predominant distal weakness, while six patients presented with atypical phenotype. However, muscle magnetic resonance imaging showed that the vastus lateralis was spared in both subgroups. In conclusion, p.D176V mutation in the GNE gene, which was the second most common mutation in Japanese patients, was the most common mutation in this cohort of Chinese patients. Novel GNE mutations found in this study expanded the mutational spectrum associated with GNE myopathy. There is phenotypic heterogeneity among patients with GNE myopathy, but muscle magnetic resonance imaging can be useful for differential diagnosis.