PMID- 10533065
OWN - NLM
STAT- MEDLINE
DCOM- 20000106
LR  - 20161124
IS  - 1059-7794 (Print)
IS  - 1059-7794 (Linking)
VI  - 14
IP  - 5
DP  - 1999
TI  - Jagged-1 mutation analysis in Italian Alagille syndrome patients.
PG  - 394-400
AB  - 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.
CI  - Copyright 1999 Wiley-Liss, Inc.
FAU - Pilia, G
AU  - Pilia G
AD  - Istituto di Ricerca sulle Talassemie ed Anemie Mediterranee CNR, Cagliari, Italy.
      pilia@vaxca1.unica.it
FAU - Uda, M
AU  - Uda M
FAU - Macis, D
AU  - Macis D
FAU - Frau, F
AU  - Frau F
FAU - Crisponi, L
AU  - Crisponi L
FAU - Balli, F
AU  - Balli F
FAU - Barbera, C
AU  - Barbera C
FAU - Colombo, C
AU  - Colombo C
FAU - Frediani, T
AU  - Frediani T
FAU - Gatti, R
AU  - Gatti R
FAU - Iorio, R
AU  - Iorio R
FAU - Marazzi, M G
AU  - Marazzi MG
FAU - Marcellini, M
AU  - Marcellini M
FAU - Musumeci, S
AU  - Musumeci S
FAU - Nebbia, G
AU  - Nebbia G
FAU - Vajro, P
AU  - Vajro P
FAU - Ruffa, G
AU  - Ruffa G
FAU - Zancan, L
AU  - Zancan L
FAU - Cao, A
AU  - Cao A
FAU - DeVirgilis, S
AU  - DeVirgilis S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Hum Mutat
JT  - Human mutation
JID - 9215429
RN  - 0 (Calcium-Binding Proteins)
RN  - 0 (Codon, Nonsense)
RN  - 0 (DNA Primers)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (JAG1 protein, human)
RN  - 0 (Jagged-1 Protein)
RN  - 0 (Membrane Proteins)
RN  - 0 (Proteins)
RN  - 0 (Serrate-Jagged Proteins)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Alagille Syndrome/*genetics
MH  - Amino Acid Sequence
MH  - Base Sequence
MH  - Calcium-Binding Proteins
MH  - Child
MH  - Codon, Nonsense
MH  - DNA/genetics
MH  - DNA Mutational Analysis
MH  - DNA Primers/genetics
MH  - Female
MH  - Frameshift Mutation
MH  - Genes, Dominant
MH  - Genotype
MH  - Humans
MH  - Intercellular Signaling Peptides and Proteins
MH  - Italy
MH  - Jagged-1 Protein
MH  - Male
MH  - Membrane Proteins
MH  - Molecular Sequence Data
MH  - *Mutation
MH  - Mutation, Missense
MH  - Phenotype
MH  - Proteins/*genetics
MH  - RNA Splicing/genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Sequence Deletion
MH  - Serrate-Jagged Proteins
EDAT- 1999/10/26 00:00
MHDA- 1999/10/26 00:01
CRDT- 1999/10/26 00:00
PHST- 1999/10/26 00:00 [pubmed]
PHST- 1999/10/26 00:01 [medline]
PHST- 1999/10/26 00:00 [entrez]
AID - 10.1002/(SICI)1098-1004(199911)14:5<394::AID-HUMU5>3.0.CO;2-1 [pii]
AID - 10.1002/(SICI)1098-1004(199911)14:5<394::AID-HUMU5>3.0.CO;2-1 [doi]
PST - ppublish
SO  - Hum Mutat. 1999;14(5):394-400. doi:
      10.1002/(SICI)1098-1004(199911)14:5<394::AID-HUMU5>3.0.CO;2-1.