PMID- 10220506
OWN - NLM
STAT- MEDLINE
DCOM- 19990607
LR  - 20220311
IS  - 0016-5085 (Print)
IS  - 0016-5085 (Linking)
VI  - 116
IP  - 5
DP  - 1999 May
TI  - Mutations in JAGGED1 gene are predominantly sporadic in Alagille syndrome.
PG  - 1141-8
AB  - BACKGROUNDS & AIMS: Mutations in the JAGGED1 gene are responsible for the
      Alagille syndrome, an autosomal dominant disorder characterized by neonatal
      jaundice, intrahepatic cholestasis, and developmental disorders affecting the
      liver, heart, vertebrae, eyes, and face. We screened a large group of patients
      for mutations in JAGGED1 and studied transmission of the mutations. METHODS: The 
      coding sequence of the JAGGED1 gene was searched by single-strand conformation
      polymorphism and sequence analysis for mutations in 109 unrelated patients with
      the Alagille syndrome and their family if available. RESULTS: Sixty-nine patients
      (63%) had intragenic mutations, including 14 nonsense mutations, 31 frameshifts, 
      11 splice site mutations, and 13 missense mutations. We identified 59 different
      types of mutation of which 54 were previously undescribed; 8 were observed more
      than once. Mutations were de novo in 40 of 57 probands. CONCLUSIONS: Most of the 
      observed mutations other than the missense mutations in JAGGED1 are expected to
      give rise to truncated and unanchored proteins. All mutations mapped to the
      extracellular domain of the protein, and there appeared to be regional hot spots,
      although no clustering was observed. Thus, the sequencing of 7 exons of JAGGED1
      would detect 51% of the mutations. Transmission analysis showed a high frequency 
      of sporadic cases (70%).
FAU - Crosnier, C
AU  - Crosnier C
AD  - INSERM Unite 347 affiliee au Centre National de la Recherche Scientifique,
      Departement de Pediatrie, Hopital de Bicetre, Le Kremlin-Bicetre, France.
FAU - Driancourt, C
AU  - Driancourt C
FAU - Raynaud, N
AU  - Raynaud N
FAU - Dhorne-Pollet, S
AU  - Dhorne-Pollet S
FAU - Pollet, N
AU  - Pollet N
FAU - Bernard, O
AU  - Bernard O
FAU - Hadchouel, M
AU  - Hadchouel M
FAU - Meunier-Rotival, M
AU  - Meunier-Rotival M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Gastroenterology
JT  - Gastroenterology
JID - 0374630
RN  - 0 (Calcium-Binding Proteins)
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)
SB  - IM
CIN - Gastroenterology. 1999 May;116(5):1257-60. PMID: 10220521
MH  - Alagille Syndrome/*genetics
MH  - Calcium-Binding Proteins
MH  - DNA Mutational Analysis
MH  - Female
MH  - Gene Frequency
MH  - Genetic Testing
MH  - Genotype
MH  - Humans
MH  - Intercellular Signaling Peptides and Proteins
MH  - Jagged-1 Protein
MH  - Male
MH  - Membrane Proteins
MH  - *Mutation
MH  - Phenotype
MH  - Polymerase Chain Reaction
MH  - Polymorphism, Genetic
MH  - Polymorphism, Single-Stranded Conformational
MH  - Proteins/*genetics
MH  - Serrate-Jagged Proteins
EDAT- 1999/04/30 00:00
MHDA- 1999/04/30 00:01
CRDT- 1999/04/30 00:00
PHST- 1999/04/30 00:00 [pubmed]
PHST- 1999/04/30 00:01 [medline]
PHST- 1999/04/30 00:00 [entrez]
AID - S0016508599004515 [pii]
AID - 10.1016/s0016-5085(99)70017-x [doi]
PST - ppublish
SO  - Gastroenterology. 1999 May;116(5):1141-8. doi: 10.1016/s0016-5085(99)70017-x.