Distal myopathies – elucidation of mechanism and development of therapy
Hybrid event - please contact chelsea.larabee@idrm.ox.ac.uk to receive the online link.
I will focus on two (non-dystrophic) distal myopathies which are relatively frequent in Japan: GNE myopathy and oculopharyngodistal myopathy (OPDM).

GNE myopathy is an autosomal recessive muscle disease characterized clinically by preferential involvement of tibialis anterior muscle and relative sparing of quadriceps, and pathologically by the presence of rimmed vacuoles, which is caused mostly by missense mutations in the GNE gene that encodes a protein with the activity of two enzymes in sialic acid biosynthesis, UDP-GlcNAC 2-epimerase and ManNAc kinase, resulting in the reduction of the sialic acid levels in serum and skeletal muscles. So far, 103 different mutations have been identified among 345 Japanese unrelated families. We treated our model mice, which showed a phenotype clinicopathologically similar to human patients, with ManNAc, NeuAc, and sialic acid conjugate, sialyllactose from around 15 weeks of age and continued to around 55 weeks. Phenotypic manifestations were almost completely suppressed, indicating that sialic acid deficiency is the cause of GNE myopathy and that the disease can be suppressed by sialic acid supplementation.

OPDM is an autosomal dominant muscle disease which is characterized by ocular and bulbar symptoms, including ptosis, ophtalmoparesis, and dysphagia, in addition to preferential distal limb muscle involvement. It is clinicopathologically similar to oculopharyngeal muscular dystrophy (OPMD) which is caused by alanine codon expansions in PABPN1. Recently, it was identified to be due to the expansion of the CGG repeats in the 5’ UTR of LRP12. Soon after that, similar 5’ UTR CGG repeat expansions in GIPC1 and NOTCH2NLC were found to be associated with OPDM. In Japan, majority of OPDM patients seem to have expansions in LRP12 while Chinese OPDM patients those in GIPC1. I will discuss detailed clinicopathological features of OPDM_LRP12 and pathological differentiation between OPDM and OPMD.
Date: 19 June 2023, 11:00 (Monday, 9th week, Trinity 2023)
Venue: John Radcliffe Hospital - Main Building, Headington OX3 9DU
Speaker: Dr Ichizo Nishino (National Center of Neurology and Psychiatry)
Organising department: Divisional Office (MSD)
Organiser contact email address: chelsea.larabee@idrm.ox.ac.uk
Host: Prof Laurent Servais (University of Oxford)
Part of: MDUK Oxford Neuromuscular Centre Seminars
Booking required?: Not required
Audience: Members of the University only
Editor: Chelsea Larabee