Consequences of JAG1 mutations

J Med Genet. 2003 Dec;40(12):891-5. doi: 10.1136/jmg.40.12.891.

Abstract

Background: Alagille syndrome (AGS) is a multi-system, autosomal dominant disorder with highly variable expressivity, caused by mutations within the Jagged1 (JAG1) gene.

Methods: We studied 53 mutation positive relatives of 34 AGS probands to ascertain the frequency of clinical findings in JAG1 mutation carriers.

Results: Eleven of 53 (21%) mutation positive relatives had clinical features that would have led to a diagnosis of AGS. Seventeen of the 53 (32%) relatives had mild features of AGS, revealed only after targeted evaluation following the diagnosis of a proband in their family. Twenty five of the 53 (47%) mutation positive relatives did not meet clinical criteria, and two of these individuals had no features consistent with AGS at all. The frequency of cardiac and liver disease was notably lower in the relatives than in the probands, characterising the milder end of the phenotypic spectrum. The characteristic facies of AGS was the feature with the highest penetrance, occurring almost universally in mutation positive probands and relatives.

Conclusions: This study has implications for genetic counselling of families with AGS and JAG1 mutations.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Alagille Syndrome / diagnosis*
  • Alagille Syndrome / genetics*
  • Calcium-Binding Proteins
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Intercellular Signaling Peptides and Proteins
  • Jagged-1 Protein
  • Male
  • Membrane Proteins
  • Middle Aged
  • Mutation*
  • Proteins / genetics*
  • Serrate-Jagged Proteins

Substances

  • Calcium-Binding Proteins
  • Intercellular Signaling Peptides and Proteins
  • JAG1 protein, human
  • Jagged-1 Protein
  • Membrane Proteins
  • Proteins
  • Serrate-Jagged Proteins

Associated data

  • OMIM/118450