title: Alagille syndrome associated with a paracentric inversion 20p12.2p13 disrupting the JAG1 gene.
abstract: Mutations in the human gene Jagged1 (JAG1) localized in 20p12 have been recently identified as causal for the anomalies found in patients with Alagille syndrome (AGS). This gene encodes a ligand for the Notch1 transmembrane receptor, which plays a key role in cell-to-cell signaling during differentiation and is conserved from C. elegans to human. We report a paracentric inversion (PAI) of chromosome 20p12.2p13 in an individual with AGS who also had alpha-1-antitrypsin deficiency. To our knowledge, this is the first published case of PAI involving the short arm of chromosome 20. Using FISH, fiberFISH, and molecular studies with a approximately 40 kb cosmid clone encompassing the entire 36 kb JAG1 gene, we demonstrate that the gene was disrupted by the inversion breakpoint between exons 5 and 6. An unusual association between two most common causes of chronic liver disease in childhood, AGS and alpha-1-antitrypsin deficiency, as well as their influence on the proband's abnormal phenotype are discussed.
authors.affiliation: Institute of Human Genetics and Medical Biology, University Halle-Wittenberg, Halle/S, Germany. pawels@bcm.tmc.edu
authors.forename: P
authors.initials: P
authors.lastname: Stankiewicz
authors.forename: J
authors.initials: J
authors.lastname: Rujner
authors.forename: C
authors.initials: C
authors.lastname: Löffler
authors.forename: A
authors.initials: A
authors.lastname: Krüger
authors.forename: M
authors.initials: M
authors.lastname: Nimmakayalu
authors.forename: B
authors.initials: B
authors.lastname: Piłacik
authors.forename: M
authors.initials: M
authors.lastname: Krajewska-Walasek
authors.forename: A
authors.initials: A
authors.lastname: Gutkowska
authors.forename: I
authors.initials: I
authors.lastname: Hansmann
authors.forename: I
authors.initials: I
authors.lastname: Giannakudis
mesh_terms: D016738:Alagille Syndrome / Q000235:genetics* / Q000473:pathology; D015139:Blotting, Southern; D002135:Calcium-Binding Proteins; D002675:Child, Preschool; D002871:Chromosome Banding; D007446:Chromosome Inversion; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics*; D004247:DNA / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D036341:Intercellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D008297:Male; D008565:Membrane Proteins; D009154:Mutation; D011506:Proteins / Q000235:genetics*; D000072099:Serrate-Jagged Proteins
chemical_list: D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D011506:Proteins; D000072099:Serrate-Jagged Proteins; D004247:DNA