Twelve novel JAG1 gene mutations in Polish Alagille syndrome patients.
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.
Jurkiewicz
Dorota
D
Children's Memorial Health Institute, Department of Medical Genetics, Warsaw, Poland. dorcik@czd.waw.pl
Popowska
Ewa
E
Gläser
Christiane
C
Hansmann
Ingo
I
Krajewska-Walasek
Małgorzata
M
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
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