Of note, 75% of Alagille syndrome-causing mutations in JAG1 are the result of frameshift, nonsense, or splice-site alterations, suggesting that a possible mechanism of the disease is JAG1 haploinsufficiency (Crosnier et al, 1999; Spinner et al, 2001), achieved in vitro by pharmacological inhibition of Notch. This evidence concerns the gene JAG1 and Alagille syndrome.