Mutation analysis of Jagged1 (JAG1) in Alagille syndrome patients

RP Colliton, L Bason, FM Lu, DA Piccoli… - Human …, 2001 - Wiley Online Library
RP Colliton, L Bason, FM Lu, DA Piccoli, ID Krantz, NB Spinner
Human mutation, 2001Wiley Online Library
Alagille syndrome (AGS) is an autosomal dominant disorder caused by mutations in
Jagged1 (JAG1), a ligand in the evolutionarily conserved Notch signaling pathway. Previous
studies have demonstrated that a wide spectrum of JAG1 mutations result in AGS. These
include total gene deletions, protein truncating, splicing and missense mutations which are
distributed across the coding region of the gene. Here we present results of JAG1 mutation
screening by SSCP and FISH in 105 patients with AGS. For these studies, new primers were …
Abstract
Alagille syndrome (AGS) is an autosomal dominant disorder caused by mutations in Jagged1 (JAG1), a ligand in the evolutionarily conserved Notch signaling pathway. Previous studies have demonstrated that a wide spectrum of JAG1 mutations result in AGS. These include total gene deletions, protein truncating, splicing and missense mutations which are distributed across the coding region of the gene. Here we present results of JAG1 mutation screening by SSCP and FISH in 105 patients with AGS. For these studies, new primers were designed for 12 exons. Mutations were identified in 63/105 patients (60%). The spectrum of the JAG1 mutations presented here is consistent with previously reported results. Eighty three percent (52/63) of the mutations were protein truncating, 11% (7/63) were missense, 2% (1/63) were splice site, and 5% (3/63) were total gene deletions demonstrable by FISH. Six of the missense mutations are novel. As has been reported previously, there is no apparent relationship between genotype and clinical phenotype. Hum Mutat 17:151–152, 2001. © 2001 Wiley‐Liss, Inc.
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