Fukutin mutations in congenital muscular dystrophies with defective glycosylation of dystroglycan in Korea

This study was aimed to identify Fukutin (FKTN)-related congenital muscular dystrophies (CMD) with defective α-dystroglycan glycosylation in Korea and to discuss their genotype–phenotype spectrum focusing on detailed brain magnetic resonance imaging (MRI) findings. FKTN mutations were found in nine of the 12 CMD patients with defective α-dystroglycan glycosylation patients (75%). Two patients were homozygous for the Japanese founder retrotransposal insertion mutation. Seven patients were heterozygous for the retrotransposal insertion mutation, five of whom carried a novel intronic mutation that activates a pseudoexon between exons 5 and 6 (c.647+2084G>T). Compared with individuals that were homozygous for the retrotransposal insertion mutation, the seven heterozygotes for the retrotransposal insertion mutation, including five patients with the novel pseudoexon mutation, exhibited a more severe clinical phenotype in terms of motor abilities and more extensive brain MRI abnormalities (i.e., a wider distribution of cortical malformation and pons and cerebellar hypoplasia). FKTN mutations are the most common genetic cause of CMD with defective α-dystroglycan glycosylation in Korea. Compound heterozygosity of the retrotransposal insertion and the novel pseudoexon mutation is the most prevalent genotype in Korea and is associated with a more severe clinical and radiological phenotype compared with homozygosity for the retrotransposal insertion mutation.