GNE mutations causing distal myopathy with rimmed vacuoles with inflammation

Abstract

The authors describe a family in which two individuals have clinical distal myopathy with rimmed vacuoles (DMRV). While the clinical and most of the pathologic features in these patients were compatible with a diagnosis of DMRV, the presence of inflammatory changes in the connective tissue between muscle fibers was not. Gene analysis revealed a compound heterozygous mutation in these individuals, characterized by V572L and I472T.

Mutation analysis of the GNE gene in Korean patients with distal myopathy with rimmed vacuoles

“…Among them, three mutations, C13S, R129Q, and V572L, have been previously reported in the Japanese population (Arai et al 2002;Kayashima et al 2002;Nishino et al 2002;Noguchi et al 2004;Saito et al 2004;Tomimitsu et al 2002Tomimitsu et al , 2004Yabe et al 2003). The V572L mutation was the most frequent mutation observed, with an estimated frequency of 68.8%, which is comparable to that in the Japanese population.…”

Clinical, pathological, and genetic mutation analysis of sporadic inclusion body myositis in Japanese people

“…We excluded 2 cases from the same family, who had distal myopathy with rimmed vacuoles caused by GNE mutations [9]. Cases of glycogenosis and lipid storage myopathy were also excluded from the study.…”

“…Mutations in this gene are also known to be responsible for distal myopathy with rimmed vacuole (DMRV), also named Nonaka myopathy (OMIM #605820), a condition that has been reported predominantly in the Japanese population and has an autosomal recessive mode of inheritance. The shared genotype and similar phenotypes of DMRV and IBM2 indicates that they are allelic disorders [9,10]. An autosomal dominant type of IBM3 (OMIM #605637), characterized by joint contractures, external ophthalmoplegia, and proximal muscle weakness, results from mutations in the gene encoding myosin heavy chain IIa (MYHC2A or MYH2); this is located on chromosome 17p13.1 [7,11,12].…”

Distal Myopathy with Rimmed Vacuoles Confirmed by Whole Exome Sequencing

“…The GNE gene is ubiquitously expressed and has two functional domains: the epimerase and the kinase domains located in the N-terminus encoding the N-actylglucosamine 2 epimerase and the C-terminus encoding the N-acetylmannosamine kinase, respectively [14,19]. Mutations in GNE have been linked to not only DMRV (MIM 605820) [27,29] but also sialuria (MIM 269921) [13,24]. In particular, many mutations of GNE have been reported to be the underlying causes of DMRV [6,9,11,14,15,18,29].…”

“…Mutations in GNE have been linked to not only DMRV (MIM 605820) [27,29] but also sialuria (MIM 269921) [13,24]. In particular, many mutations of GNE have been reported to be the underlying causes of DMRV [6,9,11,14,15,18,29].…”