title: Compound heterozygosity of a novel exon 3 frameshift (p.R357P fs*24) mutation and Y486D mutation in exon 5 of the UGT1A1 gene in a Thai infant with Crigler-Najjar syndrome type 2.
abstract: Mutations in the UGT1A1 gene cause Crigler-Najjar syndrome (CN), which causes non-hemolytic unconjugated hyperbilirubinemia, and is categorized as CN1 and CN2 according to the severity of bilirubin levels. The UGT1A1 gene is responsible for encoding the liver enzyme uridine diphosphate-glucuronosyltransferase, UGT1A1. This protein adds glucuronic acid to unconjugated bilirubin in bilirubin metabolism to form conjugated bilirubin. CN2 occurs when UGT1A1 activity is low, while CN1 is the absence of UGT1A1 activity; therefore, the CN2 phenotype is not as severe as that of CN1. Here, we report a novel allele of compound heterozygous mutations in UGT1A1 in a Thai male infant with clinical symptoms of CN2. The patient's compound heterozygosity was composed of a novel mutation, c.1069-1070insC, and the c.1456T>G mutation. The novel c.1069-1070insC mutation generated a premature stop codon in exon 4 (p.R357Pfs*24). The healthy parents were heterozygous for the c.1069-1070insC mutation (father) and c.1456T>G missense mutation (mother). Our results suggest that compound heterozygosity of the novel c.1069-1070insC and c.1456T>G (c211 G >A) missense mutation in the UGT1A1 gene played a primary role in the development of CN2 unconjugated hyperbilirubinemia.
authors.affiliation: Center of Excellence in Clinical Virology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors.forename: L
authors.initials: L
authors.lastname: Tesapirat
authors.affiliation: Center of Excellence in Clinical Virology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors.forename: P
authors.initials: P
authors.lastname: Nilyanimit
authors.affiliation: Center of Excellence in Clinical Virology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors.forename: N
authors.initials: N
authors.lastname: Wanlapakorn
authors.affiliation: Center of Excellence in Clinical Virology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand Yong.P@chula.ac.th.
authors.forename: Y
authors.initials: Y
authors.lastname: Poovorawan
mesh_terms: D001483:Base Sequence; D003414:Crigler-Najjar Syndrome / Q000175:diagnosis* / Q000235:genetics; D004252:DNA Mutational Analysis; D005091:Exons; D016368:Frameshift Mutation; D056726:Genetic Association Studies; D014453:Glucuronosyltransferase / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008297:Male; D020125:Mutation, Missense; D013785:Thailand; D000099148:UGT1A1 Enzyme
chemical_list: D014453:Glucuronosyltransferase; D000099148:UGT1A1 Enzyme