A novel stop codon mutation in exon 1 (558C>A) of the UGT1A1 gene in a Thai neonate with Crigler-Najjar syndrome type I.
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.
Center of Excellence in Clinical Virology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
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Wanlapakorn
Center of Excellence in Clinical Virology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
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Nilyanimit
Center of Excellence in Clinical Virology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
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Vorawandthanachai
Division of Neurology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
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Deesudjit
Department of Radiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
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Dumrongpisutikul
Center of Excellence in Clinical Virology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand Yong.P@chula.ac.th.
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Poovorawan
D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D018388:Codon, Terminator / Q000235:genetics*; D003414:Crigler-Najjar Syndrome / Q000235:genetics* / Q000503:physiopathology; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics*; D005260:Female; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008111:Liver Function Tests; D008279:Magnetic Resonance Imaging; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D000099148:UGT1A1 Enzyme
D018388:Codon, Terminator; D014453:Glucuronosyltransferase; D000099148:UGT1A1 Enzyme