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GENATLAS PHENOTYPE
last update : 03-07-2019
Symbol ALGS
Location 20p12.2
Name Alagille syndrome
Other name(s)
  • Alagille-Watson syndrome
  • arteriohepatic dysplasia
    • Corresponding gene JAG1
    Other symbol(s) AWS, AHD, AGS, DEL20P12
    Main clinical features polymalformative disorder affecting the liver, heart, eyes, skeleton :
  • bile duct paucity with cholestasis
  • skeletal anomalies most commonly butterfly vertebrae
  • cardiac defect most commonly valvular pulmonar stenosis
  • eye posterior embryotoxon and retinal pigmentary changes
  • characteristic facial features, frequent hypothyroidism
    • Genetic determination autosomal dominant
    Prevalence about 1/70 000
    Related entries DEL20P12, WPW2
    Function/system disorder digestive tract/liver and annex
    multisystem/generalized
    Type malformation
    Mechanism(s)
    Gene mutationChromosome rearrangementEffectComments
    various types   abnormal protein/loss of function in about 94 percent of cases, include total gene deletions, protein truncating, splicing and missense mutations which are distributed across the coding region of the gene
      deletion haploinsufficiency interstitial deletion in about 7 percent of cases
      translocation haploinsufficiency translocation or inversion with a deletion at the 20p breakpoint
    Remark(s)
  • liver defect caused by overexpression of hepatocyte growth factor
  • mutant JAG1 proteins results in an inhibition of Notch signaling, impairing either differentiation or cell migration during vascular development
    • Genotype/Phenotype correlations highly variable expressivity, even within families ; deletions encompassing JAG1 and other genes are more often associated with developmental delay and/or hearing loss ; missense mutations may be associated with mild manifestations.