title: Twelve novel JAG1 gene mutations in Polish Alagille syndrome patients.
abstract: Alagille syndrome (AGS) is an autosomal dominant disorder with developmental abnormalities of the liver, heart, eyes, vertebrae, and face. Mutations in the JAG1 (Jagged 1) gene, coding a ligand in the evolutionarily conserved Notch signaling pathway, are responsible for AGS. Here we present sixteen different JAG1 gene mutations, among them twelve novel, not described previously. Seven frameshift: c. 172_178del7 (p.Ala58fs), c.509delT (p.Leu170fs), c.1197delG (p.Val399fs), c.1485_1486delCT (p.Pro495fs), c.1809_1810insTGGG (p.Lys604fs), c.2122_2125delCAGT (p.Gln708fs), c.2753delT (p.Ile918fs); five nonsense: c.383G>A (p.Trp128X), c.496C>T (p.Glu166X), c.841C>T (p.Gln281X), c.1207C>T (p.Gln403X), c.1603C>T (p.Gln535X); two splice site: c.388-1G>C, c.3048+1_3048+2insG and two missense mutations: c.359T>A (p.Ile120Asn), c.560G>A (p.Cys187Tyr) were found. Forty percent of the changes were identified in exons 2 and 4, the remaining mutations are distributed along the entire coding sequence of the gene. Seventy-five percent of the mutations lead to creation of premature termination codons. Family studies revealed that the specific mutations were inherited in 3 out of 11 investigated cases. No correlation between genotype and phenotype was observed.
authors.affiliation: Children's Memorial Health Institute, Department of Medical Genetics, Warsaw, Poland. dorcik@czd.waw.pl
authors.forename: Dorota
authors.initials: D
authors.lastname: Jurkiewicz
authors.forename: Ewa
authors.initials: E
authors.lastname: Popowska
authors.forename: Christiane
authors.initials: C
authors.lastname: Gläser
authors.forename: Ingo
authors.initials: I
authors.lastname: Hansmann
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Krajewska-Walasek
mesh_terms: D016738:Alagille Syndrome / Q000235:genetics*; D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000235:genetics*; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D005260:Female; D016368:Frameshift Mutation; D005838:Genotype; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics*; D020125:Mutation, Missense; D017354:Point Mutation; D011044:Poland; D016133:Polymerase Chain Reaction; D017434:Protein Structure, Tertiary / Q000235:genetics; D022821:RNA Splice Sites / Q000235:genetics*; D000072099:Serrate-Jagged Proteins
chemical_list: D002135:Calcium-Binding Proteins; D018389:Codon, Nonsense; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D022821:RNA Splice Sites; D000072099:Serrate-Jagged Proteins