Jagged1 mutations in patients ascertained with isolated congenital heart defects

Ian D. Krantz, Rosemarie Smith, Ray P. Colliton, Hilary Tinkel, Elaine H. Zackai, David A. Piccoli, Elizabeth Goldmuntz, Nancy B. Spinner

Research output: Contribution to journalArticlepeer-review

127 Scopus citations


Mutations in Jagged1 cause Alagille syndrome (AGS), a pleiotropic disorder with involvement of the liver, heart, skeleton, eyes, and facial structures. Cardiac defects are seen in more than 95% of AGS patients. Most commonly these are right-sided defects ranging from mild peripheral pulmonic stenosis to severe forms of tetralogy of Fallot. AGS demonstrates highly variable expressivity with respect to all of the involved systems. This leads us to hypothesize that defects in Jagged1 can be found in patients with presumably isolated heart defects, such as tetralogy of Fallot or pulmonic stenosis. Two patients with heart defects of the type seen in AGS and their relatives were investigated for alterations in the Jagged1 gene. Jagged1 was screened by a combination of cytogenetic and molecular techniques. Patient 1 was studied because of a four-generation history of pulmonic stenosis. Molecular analysis showed a point mutation in Jagged1 in the patient and her mother. Patient 2 was investigated owing to the finding of tetralogy of Fallot and a 'butterfly' vertebra on chest radiograph first noted at age 5 years. She was found to have a deletion of chromosome region 20p12 that encompassed the entire Jagged1 gene. The identification of these two patients suggests that other patients with right-sided heart defects may have subtle findings of AGS and Jagged1 mutations.

Original languageEnglish (US)
Pages (from-to)56-60
Number of pages5
JournalAmerican journal of medical genetics
Issue number1
StatePublished - May 7 1999
Externally publishedYes


  • Alagille syndrome
  • Congenital heart disease
  • Jagged1
  • Pulmonic stenosis
  • Tetralogy of Fallot

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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