De novo mutation in JAG1 gene may be associated with jaundice-free course in ALGS

A potential de novo hot spot mutation c.2122_2125delCAGT in the JAG1 gene in children with Alagille syndrome (ALGS) may be associated with a jaundice-free course, according to data presented at the 6th World Congress of Paediatric Gastroenterology, Hepatology and Nutrition.

This retrospective study included 25 children with ALGS, 9 patients who were considered jaundice-free (patients with resolving jaundice or persistently jaundice-free after 1 year of age) and 16 patients with progressive disease (persistent jaundice or progressive cholestatic liver disease, received liver transplantation or death during follow-up).

The most common manifestation of ALGS were cardiac disease in all patients, face characteristics in 96% of patients, and cholestasis in 92% of patients. Compared to those in the progressive disease group, 9 patients in the jaundice-free group had a significantly higher native liver survival rate.

In 21 patients, 17 JAG1 mutations, including 2 large deletions, 2 inframe deletion, 5 frameshifts, 5 nonsense, and 3 splicing mutations, were found. Ten novel mutations were identified, according to the presentation. Three probands who were jaundice-free at follow-up were found to have the same de novo mutation in JAG1, c.2122_2125delCAGT.

Children with ALGS had higher serum albumin levels, lower weight-for-age Z score, and lower Metavir scores in liver pathology when receiving transplantation than age-matched children with biliary atresia at the time of liver transplantation.

Reference
Chiang CM. Clinical and genetic features of Alagille Syndrome: comparisons between patients with progressive disease versus jaundice-free course. Presented at: 6th World Congress of Paediatric Gastroenterology, Hepatology and Nutrition.