A novel stop codon mutation in exon 1 (558C > A) of the UGT1A1 gene in a Thai neonate with Crigler-Najjar syndrome type I

作者：Wanlapakorn N; Nilyanimit P; Vorawandthanachai T; Deesudjit T; Dumrongpisutikul N; Poovorawan Y^*

来源：Genetics and Molecular Research, 2015, 14(1): 419-425.

DOI：10.4238/2015.January.23.15

• Crigler-Najjar syndrome
• Kernicterus
• Mutations
• UGT1A1

Human uridine 5'-diphosphate-glucuronosyltransferases play a critical role in detoxification by conjugating bilirubin with glucoronic acid. Impaired or reduced enzymatic activity causes a spectrum of clinical disorders such as Crigler-Najjar syndrome type I (CN1), Crigler-Najjar syndrome type II, and Gilbert's syndrome. CN1 is a severe form of unconjugated hyperbilirubinemia caused by homozygous or compound heterozygous mutations in the gene for uridine 5'-diphosphate glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1), resulting in complete loss of enzyme function. Here, we report a novel homozygous mutation of UGT1A1 in a female Thai infant who was diagnosed with CN1, and her parents were found to be heterozygous carriers. The patient was homozygous for the c.558C>A mutation, which resulted in a premature stop codon in exon 1. Her asymptomatic parents were carriers of the nonsense c.558C>A mutation. Our result suggests an important role for homozygous c.558C>A mutations in the UGT1A1 gene in the development of severe unconjugated hyperbilirubinemia.

• 出版日期2015