title: Analysis of cardiovascular phenotype and genotype-phenotype correlation in individuals with a JAG1 mutation and/or Alagille syndrome.
abstract: BACKGROUND
  Cardiovascular anomalies are among the most common features of Alagille syndrome (AGS). Mutations of JAG1 are found in most individuals with AGS. This study was undertaken to determine the spectrum of cardiovascular phenotypes associated with a JAG1 mutation and/or AGS, investigate potential genotype-phenotype correlations, and begin to correlate clinical outcome with genetic pathogenesis.
  
  
  RESULTS
  We reviewed the records of 200 individuals with a JAG1 mutation or AGS. A total of 187 (94%) subjects had evidence of cardiovascular involvement. Cardiovascular anomalies were identified by imaging in 150 subjects (75%), and 37 (19%) had a peripheral pulmonary stenosis murmur with either a normal echocardiogram or no imaging study. Of the 150 subjects with anomalies confirmed by imaging, right-sided anomalies were present in 123 and left-sided anomalies in 22, with both in 12. Seventeen subjects had other anomalies. The most common abnormality was stenosis/hypoplasia of the branch pulmonary arteries (PAs), which was documented by imaging (n=111) or inferred from a peripheral pulmonary stenosis murmur (n=41) in 76% of subjects. Tetralogy of Fallot was present in 23 subjects and was accompanied by pulmonary atresia in 8. Branch PA phenotype differed between individuals with and without a JAG1 mutation. Among subjects with a JAG1 mutation, there was no correlation between the type or location of mutation and the frequency or type of cardiovascular anomaly.
  
  
  CONCLUSIONS
  More than 90% of individuals with a JAG1 mutation or AGS have cardiovascular anomalies, with branch PA stenosis the most common abnormality. Cardiovascular phenotype does not correlate with the type or location of JAG1 mutation.
authors.affiliation: Division of Cardiology, The Children's Hospital of Philadelphia and University of Pennsylvania School of Medicine, Philadelphia, Pa 19104-4318, USA.
authors.forename: Doff B
authors.initials: DB
authors.lastname: McElhinney
authors.forename: Ian D
authors.initials: ID
authors.lastname: Krantz
authors.forename: Lynn
authors.initials: L
authors.lastname: Bason
authors.forename: David A
authors.initials: DA
authors.lastname: Piccoli
authors.forename: Karan M
authors.initials: KM
authors.lastname: Emerick
authors.forename: Nancy B
authors.initials: NB
authors.lastname: Spinner
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Goldmuntz
mesh_terms: D016738:Alagille Syndrome / Q000175:diagnosis* / Q000235:genetics*; D002135:Calcium-Binding Proteins; D002648:Child; D005500:Follow-Up Studies; D005838:Genotype; D006330:Heart Defects, Congenital / Q000175:diagnosis* / Q000235:genetics*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D009154:Mutation; D010641:Phenotype; D011506:Proteins / Q000235:genetics*; D011651:Pulmonary Artery / Q000002:abnormalities; D000072099:Serrate-Jagged Proteins; D013771:Tetralogy of Fallot / Q000175:diagnosis / Q000235:genetics
chemical_list: D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D011506:Proteins; D000072099:Serrate-Jagged Proteins