A genetic disease characterized by muscle weakness, congenital brain abnormalities and eye problems as well as other defects
Glaucoma Underdeveloped retina Myopia Reduced vision Pachygyria Cobblestone cortex Cerebral atrophy Small cerebellar vermis Small brain stem Low IQ Myopia Retinal degeneration Cataracts Mental retardation Pachygyria Polymicrogyria Fluid on the brain Enlarged brain ventricles Absent corpus callosum Severe muscle weakness Hypotonia Joint contractures
MEB is caused by loss of function mutations in the gene encoding protein O-linked mannose ß1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) . O-mannosylation is a rare type of glycosylation in mammals, occurring in a limited number of brain, nerve and skeletal muscle glycoproteins . Sialyl O-mannosyl glycan is known to be a laminin-binding ligand of -dystroglycan , and POMGnT1 catalyzes the transfer of N-acetylglucosamine to O-mannose of glycoproteins.
Taniguchi et al. (2003) identified 7 disease-causing mutations in the POMGNT1 gene among 6 non-Finnish Caucasian, Japanese, and Korean patients with suspected MEB, severe FCMD (MDDGA4; 253800), or Walker-Warburg syndrome. Mutations were dispersed throughout the entire POMGNT1 gene. A slight correlation was observed between the location of the mutation and clinical severity in the brain: patients with mutations near the 5-prime terminus of the POMGNT1 coding region showed relatively severe brain symptoms such as hydrocephalus, whereas patients with mutations near the 3-prime terminus had milder phenotypes. The authors suggested that MEB may exist in populations outside of Finland, and that the clinical spectrum of MEB may be broader than recognized theretofore.