Myelin oligodendrocyte gene polymorphisms and childhood multiple sclerosis.
Myelin oligodendrocyte glycoprotein (MOG) is a quantitatively minor glycoprotein of the CNS localized preferentially on the outermost myelin lamellae and the oligodendrocyte plasma membrane. In several animal models, MOG displays highly immunogenic properties by inducing a severe multiple sclerosis-like disease, characterized by inflammatory demyelinating lesions. Immunologic findings implicate MOG as a target autoantigen in multiple sclerosis. We have performed a molecular study on the MOG gene by sequencing the promotor and the entire coding region, as well as the exon-intron boundaries, in 75 children with multiple sclerosis. A total of five unknown polymorphic sites in the promotor region not affecting any of the putative cis-acting transcriptional regulation motifs as well as nine additional base changes in four different exons each with similar distribution in patients and controls (n = 100) were detected. Exon 2 coding for the Ig-like domain revealed two rare heterozygous missense mutations, possibly altering favorable conformational epitopes (P43H; R66P). P43 is part of the encephalitogenic epitope MOG(35-55). A putative C1q binding site in the C"-D loop of the Ig superfamily motif encompasses R66. In conclusion, the polymorphisms observed do not provide evidence to support a significant role for MOG in multiple sclerosis susceptibility.
Ohlenbusch
Andreas
A
Abteilung Pädiatrie, Schwerpunkt Neuropädiatrie, Georg-August-Universität, 37075 Göttingen, Germany.
Pohl
Daniela
D
Hanefeld
Folker
F
D024506:5' Flanking Region / Q000235:genetics; D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D009103:Multiple Sclerosis / Q000235:genetics*; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000235:genetics*; D063308:Myelin-Oligodendrocyte Glycoprotein; D011110:Polymorphism, Genetic
C571326:MOG protein, human; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein