Check out our July newsletter
JAG1 (NM_000214.2) encodes the Jagged-1 protein, which is a ligand for the Notch receptor and is involved in cell differentiation and morphogenesis. JAG1 is located at 20p12.2 and is composed of 26 coding exons. Autosomal dominant mutations in the JAG1 gene are a leading cause of Alagille syndrome (AGS), a multisystem disorder with an estimated incidence of at least 1/70,000. Diagnostic criteria require three of the following five major features: cholestasis due to bile duct paucity, cardiac defect (often pulmonic stenosis or tetralogy of Fallot), anterior chamber defects of the eye (especially posterior embryotoxon), butterfly vertebrae or other skeletal abnormalities, and characteristic facial features. Most patients are diagnosed in infancy. Mortality is 10% with early deaths, due to cardiac or severe liver disease and late mortality from vascular accidents. Penetrance is high, but diagnosis may be complicated by the large proportion of de novo mutations (50-70%) and highly variable clinical expression even within the same family. Severity ranges from multisystem involvement with critical liver or cardiac disease, to isolated cardiac defects, to subclinical vertebral or facial changes.