781 Crigler-Najjar Syndrome Type Ii Caused by Homozygous Double Mutation [T1456G, G211A] of Ugt1A1 Gene in a Taiwanese Sibling

Abstract

Objective: This study aimed to analyze the mutations of UDP-glucuronosyltransferase 1A1 (UGT1A1) gene in a Taiwanese family.

Patients and Methods: Two brothers aged 24 and 2 months, respectively were born to a Chinese mother who married to a Taiwanese man. They had profound unconjugated hyperbilirubinemia in the newborn period (30.7 and 25.2 mg/dL, respectively). The liver function, hemoglobin and glucose-6-phosphate dehydrogenase levels were within normal limit. They both received intensive phototherapy and the serum bilirubin level gradually decreased to 6-10 mg/dL. The blood samples of the brothers and their parents were sent for DNA analysis including the promoter area of the UGT1A1 gene, exons 1-4, the coding region of exon 5, and their flanking intronic regions. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct DNA sequencing were used.

Results: The PCR results for the UGT1A1 gene showed homozygous G > A substitution at nucleotide 211 in exon 1 and homozygous T > G substitution at nucleotide 1456 in exon 5 (Gly⁷¹ Arg plus Tyr⁴⁸⁶ Asp) in both patients. No other variation was detected in the UGT1A1 gene. Analyzing the UGT1A1 gene of the parents showed a homozygous 211G > A plus a heterozygous 1456 T > G variations in their father and a heterozygous 211G > A plus a heterozygous 1456 T > G variations in their mother. All of the tests were confirmed by the direct gene sequence.

Conclusion: Double homozygous mutation [T1456G, G211A] of UGT1A1 gene is rare in CN-2 and is a novel mutation in Taiwanese children.

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