Crigler-Najjar syndrome (CN) type II is characterized by severe chronic nonhemolytic unconjugated hyperbilirubinemia due to reduced hepatic bilirubin UDP-glucuronosyl-transferase (UGT) activity. Two bilirubin UGT isozymes, UGT1A and UGT1D, have been identified. We analyzed the DNA sequence of the bilirubin UGT genes in a 5-year-old Japanese male patient with CN type II, who had consanguineous parents. Point mutations were found on exons 1 of the UGT1A and UGT1D genes. The abnormalities were single nucleotide substitutions of G by A and of T by C at base position 211 of UGT1A cDNA and at base position 395 of the UGT1D, respectively. We found another single nucleotide substitution of T by G on exon 5 common to both genes at base position 1456 of the UGT1A cDNA or 1459 of the UGT1D cDNA. These three mutations result in changes of glycine to arginine and of tyrosine to aspartic acid at amino acid positions 71 and 486 of the UGT1A protein, and of leucine to proline and of tyrosine to aspartic acid at amino acid positions 132 and 487 of the UGT1D protein, respectively. Our patient was homozygous for all defects and his parents and elder brother were heterozygous for all defective alleles. The findings suggest that the CN Type II is inherited as an autosomal recessive trait.
[ hide abstract ]
Reminder: you don't need to add entities already covered in variant annotations -- they'll be added automatically.