Jagged-1 mutation analysis in Italian Alagille syndrome patients

Giuseppe Pilia, Manuela Uda, Dolores Macis, Fulvia Frau, Laura Crisponi, Fiorella Balli, Cristiana Barbera, Carla Colombo, Tullio Frediani, Rosanna Gatti, Raffaele Iorio, M. Grazia Marazzi, Matilde Marcellini, Salvatore Musumeci, Gabriella Nebbia, Pietro Vajro, Giuseppe Ruffa, Lucia Zancan, Antonio Cao, Stefano De Virgilis

Research output: Contribution to journalArticlepeer-review


Alagille syndrome (AGS) is an autosomal dominant disorder with developmental abnormalities affecting the liver, heart, eyes, vertebrae, and craniofacial region. The Jagged-1 (JAG1) gene, which encodes a ligand of Notch, has recently been found mutated in AGS. In this study, mutation analysis of the JAG1 gene performed on 20 Italian AGS patients led to the identification of 15 different JAG1 mutations, including a large deletion of the 20p12 region, six frameshift, three nonsense, three splice-site, and two missense mutations. The two novel missense mutations were clustered in the 5' region, while the remaining mutations were scattered throughout the gene. The spectrum of mutations in Italian patients was similar to that previously reported. We also studied in detail a complex splice site mutation, 3332dupl8bp, which was shown to lead to an abnormal JAG1 mRNA, resulting in a premature stop codon. With the exception of the missense mutations, the majority of the JAG1 mutations are therefore likely to produce truncated proteins. Since the phenotype of the patient with a complete deletion of the JAG1 gene is indistinguishable from that of patients with intragenic mutations, our study further supports the hypothesis that haploinsufficiency is the most common mechanism involved in AGS pathogenesis. Furthermore, our data confirmed the absence of a correlation between the genotype of the JAG1 gene and the AGS phenotype.

Original languageEnglish
Pages (from-to)394-400
Number of pages7
JournalHuman Mutation
Issue number5
Publication statusPublished - 1999


  • AGS
  • Alagille syndrome
  • Genotype-phenotype
  • JAG1
  • Jagged-1

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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