Human Molecular Genetics, 2003, Vol. 12, No. 5 527-534
© 2003 Oxford University Press
Worldwide distribution and broader clinical spectrum of muscle–eye–brain disease
1Division of Functional Genomics, Department of Post-Genomics and Diseases, Osaka University Graduate School of Medicine, 2-2-B9 Yamadaoka, Suita, Osaka 565-0871, Japan, 2Department of Pediatrics, Tokyo Women's Medical University, School of Medicine, Tokyo, Japan, 3Department of Pediatrics, Dokkyo University School of Medicine, Tochigi, Japan, 4Division of Pediatric Neurology, Miyagi Prefectural Takuto Rehabilitation Centre for Children, Sendai, Japan, 5Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan, 6Glycobiology Research Group, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan, 7Department of Pediatrics, Sungkyunkwan University, Samsung Medical Center, Seoul, South Korea, 8Institute of Neurological Science, The National Research Council of Italy, Catania, Italy, 9Pediatric Clinic, University of Catania, Catania, Italy, 10Division of Neurometabolic Disorders, Ghent University Hospital, Ghent, Belgium, 11Department of Pediatric Pathology and 12Department of Pediatric Neurology, Hacettepe Children's Hospital, Ankara, Turkey and 13Department of Pediatrics and Pediatric Neurology, University of Essen, Essen, Germany
Received November 1, 2002; Accepted December 19, 2002
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 ß1,2-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.
* To whom correspondence should be addressed at: 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. Tel: +81 668793380; Fax: +81 668793389; Email: toda{at}clgene.med.osaka-u.ac.jp
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