title: Fukutin mutations in congenital muscular dystrophies with defective glycosylation of dystroglycan in Korea.
abstract: This study was aimed to identify Fukutin (FKTN)-related congenital muscular dystrophies (CMD) with defective alpha-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 alpha-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 alpha-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.
authors.affiliation: Department of Pediatrics, Seoul National University Children's Hospital, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Bung Chan
authors.initials: BC
authors.lastname: Lim
authors.forename: Chang-Seok
authors.initials: CS
authors.lastname: Ki
authors.forename: Jong-Won
authors.initials: JW
authors.lastname: Kim
authors.forename: Anna
authors.initials: A
authors.lastname: Cho
authors.forename: Min Jung
authors.initials: MJ
authors.lastname: Kim
authors.forename: Hee
authors.initials: H
authors.lastname: Hwang
authors.forename: Ki Joong
authors.initials: KJ
authors.lastname: Kim
authors.forename: Yong Seung
authors.initials: YS
authors.lastname: Hwang
authors.forename: Woong Yang
authors.initials: WY
authors.lastname: Park
authors.forename: Yun-Jung
authors.initials: YJ
authors.lastname: Lim
authors.forename: In One
authors.initials: IO
authors.lastname: Kim
authors.forename: Jun Su
authors.initials: JS
authors.lastname: Lee
authors.forename: Jong Hee
authors.initials: JH
authors.lastname: Chae
mesh_terms: D001921:Brain / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D049030:Dystroglycans / Q000235:genetics* / Q000378:metabolism; D005091:Exons / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D006031:Glycosylation; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007150:Immunohistochemistry; D007438:Introns / Q000235:genetics; D008279:Magnetic Resonance Imaging; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009136:Muscular Dystrophies / Q000235:genetics* / Q000378:metabolism; D016254:Mutagenesis, Insertional; D010641:Phenotype; D056910:Republic of Korea / Q000453:epidemiology; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C113587:FKTN protein, human; D008565:Membrane Proteins; D049030:Dystroglycans; D004247:DNA