A novel deletion with two pathogenic variants of UGT1A1 causing Crigler-Najjar syndrome in two unrelated Chinese

Two Chinese female infants from two unrelated families were diagnosed with Crigler-Najjar syndromes-I (CNS-I) and CNS-II respectively. The CNS-I patient had Serum Total Bilirubin Concentration (STBC) peaked at 26.1 mg/dL. She was not responsive to Phenobarbital and received liver transplantation at 2-year-old. The CNS-II patient's STBC fluctuated between 10.2 mg/dL and 17.4 mg/dL and had a milder phenotype. Sequencing of Uridine Diphosphate Glucuronosyl Transferase 1A1 (UGT1A1) revealed the CNS-I patient carried a heterozygous pathogenic variant in c.392 T > C (p.Leu131Pro) and the CNS-II patient carried a heterozygous pathogenic variant in c.1456 T > G (p.Tyr486Asp). Furthermore, a novel deletion spanning exons 2-4 of UGT1A1 were detected in both patients. We studied two family members' genotyping results of UGT1A1 to clarify the inheritance of this microdeletion. To our knowledge, this is probably the first time showing 2 CNS cases both carrying compound heterozygous variations of a known pathogenic variant and a novel microdeletion.