P3.1 Brown–Vialetto–Van Laere and Fazio Londe overlap sindromes: A clinical, biochemical and genetic study in 6 patients

Abstract

Myofibrillar myaopathy (MFM) is a group of genetically heterogeneous disorders characterized by protein aggregates in muscle fibers associated with markedly disorganized myofibrils. To date, 7 causative genes were identified including DES, CRYAB, ZASP, MYOT, FLNC, BAG3, and FHL1. To know the character of Japanese patients with MFM. We performed mutation screening in 114 Japanese patients with MFM. Clinical and pathological findings were analyzed. In our series, number of patients with mutations in DES, ZASP, MYOT, FLNC, BAG3, and FHL1 were 6, 6, 4, 6, 2, and 6, respectively. No patient with CRYAB mutation was identified. Clinical and pathological characterization of these patients was performed. We further screened VCP mutation and identified 5 patients in our series. One patient show cerebellar signs, but the remaining four patients show no clinical symptoms for Paget’s disease of bone and front-temporal dementia. From the pathological points of view, VCP could also include a causative gene for MFM. Clinical features of MFM patients are quite variable. Frequency of each causative gene was different from the previous reports. In our series, no mutation was identified in 69% of the MFM patients. Additional responsible genes should be identified.