Parental mosaicism of JAG1 mutations in families with Alagille syndrome

The Alagille syndrome (AGS), a congenital disorder affecting liver, heart, skeleton and eye in association with a typical face, is an autosomal domina nt disease with nearly complete penetrance and variable expression. AGS is caused by mutations in the developmentally important JAG1 gene. In our muta tion screening, where 61 mutations in JAG1 were detected, we identified fiv e cases where mosaicism is present. Our results point to a significant freq uency of mosaicism for JAG1 mutations in AGS of more than 8.2%. Because mos aicism may be associated with a very mild phenotype, the appropriate diagno sis of AGS and consequently the determination of the recurrence risk can be complicated.