A homozygous mutation in a Chinese man with Crigler-Najjar syndrome type II and a family genetic analysis.

Objective: To investigate the family genetic background of a 22-year-old man with Crigler-Najjar syndrome type II (CN-II).

Methods: After the proband (patient) with CN-II was diagnosed by liver function tests, a low calorie intake test and an oral phenobarbital enzyme-induction trial, blood samples were collected from 11 family members for identifying DNA gene groups. Exons 1-5 of the UGT1A1 gene were amplified by polymerase chain reaction (PCR) and mutations of the UGT1A1 gene were screened by a direct DNA sequencing.

Results: The serum unconjugated bilirubin increased in the proband from 156.4 micromol/L to 243.5 micromol/L after he started a low calorie intake, and it decreased to 51.8 micromol/L within a month of taking oral phenobarbital daily. Both functional tests and ultrasonographic images of the liver were normal except for the unconjugated hyperbilirubinemia. A missense mutation of Tyr486Asp at exon 5 in the UGT1A1 gene and a homozygous mutation were confirmed in the proband. Heterozygous mutations were found in his parents, his younger sister and three great-uncles, while no mutation of the UGT1A1 gene was detected in the remaining four family members.

Conclusion: A missense mutation of Tyr486Asp is considered to be the cause of the CN-II in this patient. It is a recessive trait that is autosomally inherited in this family. No influence of the mutation was found on the response elements for phenobarbital in the promoter region.