Alagille syndrome (AGS) is an autosomal dominant disorder, associated with abnormalities of the liver, heart, eye, skeleton, and a characteristic facial appearance. JAG1 is the causal gene of AGS. Mutations of this gene have been documented in 65 - 70% of individuals with AGS. JAG1 is part of the Notch pathway, an extremely conserved and widely spread mechanism regulating cell fates. Mutations in other genes in the Notch pathway are discussed to give rise to AGS in these 30 - 35% of patients where no JAG1 mutation was detected. Fringe Gene [Lunatic Fringe Gene (LFNG), Manic Fringe Gene (MFNG) und Radical Fringe Gene (RFNG)] products, another part of the Notch pathway, modulate the effect of JAG1. Therefore Fringe Genes are candidate genes for AGS. The present study examined possible correlations between AGS and mutations in the coding regions of the Fringe Genes. The sequences of the human Fringe Genes were completed by in silico analyses, BAC bank screening and sequencing. The genomic structure of the LFNG was discovered. Using single stranded conformational polymorphism analysis 38 AGS affected individuals without mutation in JAG1 were screened for mutations within the coding regions of the Fringe Genes. Unscreened stayed exon1 and exon8 of the LFNG and exon1 of the RFNG. Some single nucleotide polymorphisms have been identified: In LFNG c:433-106C→T, c:433-78C→T, c:733-51C→A, c:733-36C→T, c:969G→A, c:985-53G→A, c:985-37G→A, in RFNG c:460A→C, c:574-5C→T, c:993+102G→A and in MFNG c:648-56C→T. The results suggest no connection between AGS and mutations in the coding regions of the Fringe Genes. |