Anti-FKTN (aa 29-138) polyclonal antibody

Mutations in genes required for the glycosylation of alpha-dystroglycan lead to muscle and brain diseases known as dystroglycanopathies. However, the precise structure and biogenesis of the assembled glycan are not completely understood. Here we report that three enzymes mutated in dystroglycanopathies can collaborate to attach ribitol phosphate onto a-dystroglycan. Specifically, we demonstrate that isoprenoid synthase domain-containing protein (ISPD) synthesizes CDP-ribitol, present in muscle, and that both recombinant fukutin (FKTN) and fukutin-related protein (FKRP) can transfer a ribitol phosphate group from CDP-ribitol to alpha-dystroglycan. We also show that ISPD and FKTN are essential for the incorporation of ribitol into alpha-dystroglycan in HEK293 cells. Glycosylation of alpha-dystroglycan in fibroblasts from patients with hypomorphic ISPD mutations is reduced. We observe that in some cases glycosylation can be partially restored by addition of ribitol to the culture medium, suggesting that dietary supplementation with ribitol should be evaluated as a therapy for patients with ISPD mutations.

Fukuyama congenital muscular dystrophy (FCMD) is an autosomal recessive disorder with early onset severe muscular dystrophy and neuronal migration disturbances. Although FCMD is the second most common muscular dystrophy in Japan, there has been no report of FCMD in Korea. Recently, we found a 10-year-old Korean boy with characteristic clinical features of FCMD. A PCR-based diagnostic method to detect the 3-kb retrotransposal insertion in the 3' non-coding region of the fukutin (FKTN) gene revealed that the patient was homozygous for the insertion Mutation and his parents were heterozygous carriers of the same mutation. To the best of our knowledge, this is the first report of a clinically and genetically confirmed Korean patient with FCMD and the first non-Japanese patient carrying homozygous founder insertion mutation. (C) 2009 Elsevier B.V. All rights reserved.