title: Two unrelated patients with rare Crigler-Najjar syndrome type I: two novel mutations and a patient with loss of heterozygosity of UGT1A1 gene.
abstract: Crigler-Najjar syndrome type I (CN-I) is the most severe type of hereditary unconjugated hyperbilirubinemia. It is caused by homozygous or compound heterozygous mutations of the UDP-glycuronosyltransferase gene (UGT1A1) on chromosome 2q37. Two patients clinically diagnosed with CN-I were examined in this paper. We sequenced five exons and their flanking sequences, specifically the promoter region of UGT1A1, of the two patients and their parents. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to determine the UGT1A1 gene copy number of one patient. In patient A, two mutations, c.239_245delCTGTGCC (p.Pro80HisfsX6; had not been reported previously) and c.1156G>T (p.Val386Phe), were identified. In patient B, we found that this patient had lost heterozygosity of the UGT1A1 gene by inheriting a deletion of one allele, and had a novel mutation c.1253delT (p.Met418ArgfsX5) in the other allele. In summary, we detected three UGT1A1 mutations in two CN-I patients: c.239_245delCTGTGCC (p.Pro80HisfsX6), c.1253delT (p.Met418ArgfsX5), and c.1156G>T (p.Val386Phe). The former two mutations are pathogenic; however, the pathogenic mechanism of c.1156G>T (p.Val386Phe) is unknown.
authors.affiliation: Department of Medical Genetics, Capital Institute of Pediatrics, Beijing 100020, China; Department of Gastroenterology, Affiliated Children's Hospital, Capital Institute of Pediatrics, Beijing 100020, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Yu-jin
authors.initials: YJ
authors.lastname: Qu
authors.forename: Xue-mei
authors.initials: XM
authors.lastname: Zhong
authors.forename: Yan-yan
authors.initials: YY
authors.lastname: Cao
authors.forename: Li-min
authors.initials: LM
authors.lastname: Jin
authors.forename: Jin-li
authors.initials: JL
authors.lastname: Bai
authors.forename: Xin
authors.initials: X
authors.lastname: Ma
authors.forename: Yu-wei
authors.initials: YW
authors.lastname: Jin
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: Yan-ling
authors.initials: YL
authors.lastname: Zhang
authors.forename: Fang
authors.initials: F
authors.lastname: Song
mesh_terms: D003414:Crigler-Najjar Syndrome / Q000175:diagnosis* / Q000235:genetics*; D017809:Fatal Outcome; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D007223:Infant; D019656:Loss of Heterozygosity / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D035583:Rare Diseases / Q000175:diagnosis / Q000235:genetics; D000099148:UGT1A1 Enzyme
chemical_list: D005819:Genetic Markers; D014453:Glucuronosyltransferase; D000099148:UGT1A1 Enzyme
keywords: Crigler-Najjar syndrome type I (CN-I); Hyperbilirubinemia; Loss of heterozygosity; Mutation; UDP-glycuronosyltransferase gene (UGT1A1)