An infant has prolonged jaundice with conjugated hyperbilirubinemia, pruritus, and pale stools. Examination shows a systolic murmur loudest in the back and intercostal regions, and spine radiographs reveal butterfly vertebrae. Liver biopsy shows a paucity of interlobular bile ducts. Which gene is mutated?
- A CFTR
- B ATP8B1
- C JAG1 ✓
- D ABCB4
Correct answer: C. JAG1
Explanation
Alagille syndrome is an autosomal dominant condition caused by mutations in JAG1, a Notch receptor ligand, in over 90 percent of cases, with a few due to NOTCH2 mutations. It combines chronic cholestasis from bile duct paucity, peripheral pulmonic stenosis as the commonest cardiac lesion, butterfly vertebrae, posterior embryotoxon of the eye, and characteristic facies with deep-set eyes and a pointed chin. ATP8B1 causes benign recurrent intrahepatic cholestasis, a different entity.
Reference: Nelson Textbook of Pediatrics, 21st ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.