Two Novel Mutations in the Gene in Pediatric Patients with Alagille Syndrome: The First Case Series in Czech Republic.

Background: Alagille syndrome (ALGS) is a highly variable multisystem disorder inherited in an autosomal dominant pattern with incomplete penetration. The disorder is caused by mutations in the gene, only rarely in the gene, which gives rise to malformations in multiple organs. Bile duct paucity is the main characteristic feature of the disease.

Methods: Molecular-genetic examination of genes and in four probands of Czech origin who complied with the diagnostic criteria of ALGS was performed using targeted next-generation sequencing of genes and Segregation of variants in a family was assessed by Sanger sequencing of parental DNA.

Results: Mutations in the gene were confirmed in all four probands. We identified two novel mutations: c.3189dupG and c.1913delG. Only in one case, the identified mutation was de novo. None of the parents carrying pathogenic mutation was diagnosed with ALGS.

Conclusion: Diagnosis of the ALGS is complicated due to the absence of clear genotype-phenotype correlations and the extreme phenotypic variability in the patients even within the same family. This fact is of particular importance in connection to genetic counselling and prenatal genetic testing.