G.P.5.03 Genotype–phenotype correlation of DMRV/hIBM patient in Japan

Abstract

Background: Distal myopathy with rimmed vacuoles (DMRV)/hereditary inclusion body myopathy (hIBM) is an autosomal recessive muscle disease caused by mutations in GNE gene encoding UDP-N-acetylglucosamine 2 epimerase/ N-acetylmannosamine kinase. This disease is clinically characterized by onset in early adulthood, preferential involvement of tibialis anterior muscle and quadriceps sparing. Various GNE mutations have been identified in DMRV/hIBM patients from a variety of ethnic groups. Nevertheless, the genotype-phenotype correlation has not been well established. In addition, the prevalence of DMRV/hIBM has not been well established. Objectives: To establish genotype–phenotype correlation in DMRV/hIBM and to estimate the prevalence of the disease in Japan. Method: We confirmed GNE mutations in 91 Japanese DMRV/hIBM patients and compared clinical features among them. We calculated the frequency of each mutation and estimated the prevalence of the disease in Japan by comparing with prevalence of Duchenne muscular dystrophy. Result: In Japanese population, of the two most mutations were p.V572L and p.D176V, accounting for 54% and 22% of alleles, respectively. There was no obvious relationship between genotype and phenotype. Estimated prevalence of DMRV/hIBM was 1.71 to 3.05 per million in Japanese populations. Conclusion: p.V572L accounts for more than 50% of alleles. Clear genotype-phenotype correlation is not seen. The number of DMRV/hIBM patients in Japan is estimated to be 200–400.