title: Worldwide distribution and broader clinical spectrum of muscle-eye-brain disease.
abstract: Muscle-eye-brain disease (MEB), an autosomal recessive disorder prevalent in Finland, is characterized by congenital muscular dystrophy, brain malformation and ocular abnormalities. Since the MEB phenotype overlaps substantially with those of Fukuyama-type congenital muscular dystrophy (FCMD) and Walker-Warburg syndrome (WWS), these three diseases are thought to result from a similar pathomechanism. Recently, we showed that MEB is caused by mutations in the protein O-linked mannose beta1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) gene. We describe here the identification of seven novel disease-causing mutations in six of not only non-Finnish Caucasian but also Japanese and Korean patients with suspected MEB, severe FCMD or WWS. Including six previously reported mutations, the 13 disease-causing mutations we have found thus far are dispersed throughout the entire POMGnT1 gene. We also observed a slight correlation between the location of the mutation and clinical severity in the brain: patients with mutations near the 5' terminus of the POMGnT1 coding region show relatively severe brain symptoms such as hydrocephalus, while patients with mutations near the 3' terminus have milder phenotypes. Our results indicate that MEB may exist in population groups outside of Finland, with a worldwide distribution beyond our expectations, and that the clinical spectrum of MEB is broader than recognized previously. These findings emphasize the importance of considering MEB and searching for POMGnT1 mutations in WWS or other congenital muscular dystrophy patients worldwide.
authors.affiliation: Division of Functional Genomics, Department of Post-Genomics and Diseases, Osaka University Graduate School of Medicine, 2-2-B9 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Kiyomi
authors.initials: K
authors.lastname: Taniguchi
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Kayoko
authors.initials: K
authors.lastname: Saito
authors.forename: Hideo
authors.initials: H
authors.lastname: Yamanouchi
authors.forename: Akira
authors.initials: A
authors.lastname: Ohnuma
authors.forename: Yukiko K
authors.initials: YK
authors.lastname: Hayashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Manya
authors.forename: Dong Kyu
authors.initials: DK
authors.lastname: Jin
authors.forename: Munhyang
authors.initials: M
authors.lastname: Lee
authors.forename: Enrico
authors.initials: E
authors.lastname: Parano
authors.forename: Raffaele
authors.initials: R
authors.lastname: Falsaperla
authors.forename: Piero
authors.initials: P
authors.lastname: Pavone
authors.forename: Rudy
authors.initials: R
authors.lastname: Van Coster
authors.forename: Beril
authors.initials: B
authors.lastname: Talim
authors.forename: Alice
authors.initials: A
authors.lastname: Steinbrecher
authors.forename: Volker
authors.initials: V
authors.lastname: Straub
authors.forename: Ichizo
authors.initials: I
authors.lastname: Nishino
authors.forename: Haluk
authors.initials: H
authors.lastname: Topaloglu
authors.forename: Thomas
authors.initials: T
authors.lastname: Voit
authors.forename: Tamao
authors.initials: T
authors.lastname: Endo
authors.forename: Tatsushi
authors.initials: T
authors.lastname: Toda
mesh_terms: D000328:Adult; D001921:Brain / Q000002:abnormalities*; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005124:Eye Abnormalities / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D008969:Molecular Sequence Data; D009136:Muscular Dystrophies / Q000453:epidemiology* / Q000235:genetics; D010375:Pedigree; D010641:Phenotype