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.

Keywords: GNE myopathy; homozygous; missense mutation; the GNE gene.

Figure 1

Pedigree data of a GNE myopathy family. A, Pedigree of the family with GNE myopathy. N: normal; M: the GNE c.1627G>A (p.V543M) mutation. Arrow indicates the proband. B, Sequence of homozygous c.1627G>A (p.V543M) variant. C, Sequence of heterozygous c.1627G>A (p.V543M) variant. D, Sequence of a normal control

Figure 2

MRI in patients (II:3 and II:5) revealed serious fatty replacement in posterior and medial compartments of the thigh muscles and almost all lower leg muscles, which also presented in the buttock muscles of the patient (II:3). (A and B), axial T1‐weighted and axial PDw SPAIR MRI of thigh, lower leg and buttock muscles in patient (II:3). (C and D), axial T1‐weighted and axial PDw SPAIR MRI of thigh and lower leg muscles in patient (II:5)

Figure 3

Conservation analysis of the GNE p.Val543 amino acid residue