Reported by Susan Aldridge, PhD, medical journalist

New research has found genetic mutations linked to Alagille syndrome which may be important in kidney disease.
Alagille syndrome, estimated to affect around one in 20,000, is a complex disorder affecting the liver, heart, eyes, face and skeleton. Symptoms range from mild to life-threatening. Researchers at the Children's Hospital of Philadelphia have been investigating the genetic basis of Alagille syndrome. They have found that mutations in a gene called JAG1 are involved in 94 per cent of cases. JAG1 is part of a molecular signalling pathway which is operative in early development.

Now they have looked at 11 patients with Alagille syndrome who did not have the JAG1 mutation. Two had mutations in NOTCH2, a protein related to JAG1. The two patients had three family members who were also mildly affected by Alagille syndrome and they had the same mutations. All five individuals had kidney disease. This is the first study to show that mutations in NOTCH2 cause disease. The researchers now hope to better characterise the genetic influences underlying kidney disease in a wider population of patients.

Source
American Journal of Human Genetics July 2006