BACKGROUND: This study aimed to evaluate the genetic effect of the NR1H4 gene in the pathogenesis of idiopathic infantile cholestasis of Chinese subjects in Guangxi, China. METHODS: Seventy-eight patients with idiopathic infantile cholestasis served as a study group and 95 infants without cholestasis as controls. Genomic DNA was extracted from peripheral venous blood leucocytes by phenol chloroform procedures. Polymerase chain reaction (PCR) was used to amplify all coded exons of NR1H4, and single-strand conformation polymorphism (SSCP) was used to analyze all amplification fragments. The PCR products with abnormal bands in SSCP were sequenced using an ABI 3100 sequencer. RESULTS: A novel heterozygous termination codon mutation in NR1H4 exon 5 (NR1H4 R176X, CGA-TGA) was found in one of the 78 patients. The patient with mutation R176X had high levels of bilirubin, alanine aminotransferase, γ-glutamyltransferase, cirrhosis and ascites despite biliary tract flushing procedures and drug therapy. In the other patients and controls, no mutation was detected. CONCLUSIONS: Heterozygous termination codon mutation of NR1H4 R176X was found in idiopathic infantile cholestasis. The novel mutation is useful to establish particular characteristics for differential diagnosis of idiopathic infantile cholestasis and to determine the influence of such gene defects in the prognosis.
BACKGROUND: This study aimed to evaluate the genetic effect of the NR1H4 gene in the pathogenesis of idiopathic infantile cholestasis of Chinese subjects in Guangxi, China. METHODS: Seventy-eight patients with idiopathic infantile cholestasis served as a study group and 95 infants without cholestasis as controls. Genomic DNA was extracted from peripheral venous blood leucocytes by phenol chloroform procedures. Polymerase chain reaction (PCR) was used to amplify all coded exons of NR1H4, and single-strand conformation polymorphism (SSCP) was used to analyze all amplification fragments. The PCR products with abnormal bands in SSCP were sequenced using an ABI 3100 sequencer. RESULTS: A novel heterozygous termination codon mutation in NR1H4 exon 5 (NR1H4R176X, CGA-TGA) was found in one of the 78 patients. The patient with mutation R176X had high levels of bilirubin, alanine aminotransferase, γ-glutamyltransferase, cirrhosis and ascites despite biliary tract flushing procedures and drug therapy. In the other patients and controls, no mutation was detected. CONCLUSIONS: Heterozygous termination codon mutation of NR1H4R176X was found in idiopathic infantile cholestasis. The novel mutation is useful to establish particular characteristics for differential diagnosis of idiopathic infantile cholestasis and to determine the influence of such gene defects in the prognosis.
Authors: B Goodwin; S A Jones; R R Price; M A Watson; D D McKee; L B Moore; C Galardi; J G Wilson; M C Lewis; M E Roth; P R Maloney; T M Willson; S A Kliewer Journal: Mol Cell Date: 2000-09 Impact factor: 17.970
Authors: Peter Kovacs; Rahel Kress; Jacqueline Rocha; Ulrike Kurtz; Juan Francisco Miquel; Flavio Nervi; Nahum Méndez-Sánchez; Misael Uribe; Hans H Bock; Ramin Schirin-Sokhan; Michael Stumvoll; Joachim Mössner; Frank Lammert; Henning Wittenburg Journal: J Hepatol Date: 2007-10-01 Impact factor: 25.083
Authors: Natalia Gomez-Ospina; Carol J Potter; Rui Xiao; Kandamurugu Manickam; Mi-Sun Kim; Kang Ho Kim; Benjamin L Shneider; Jennifer L Picarsic; Theodora A Jacobson; Jing Zhang; Weimin He; Pengfei Liu; A S Knisely; Milton J Finegold; Donna M Muzny; Eric Boerwinkle; James R Lupski; Sharon E Plon; Richard A Gibbs; Christine M Eng; Yaping Yang; Gabriel C Washington; Matthew H Porteus; William E Berquist; Neeraja Kambham; Ravinder J Singh; Fan Xia; Gregory M Enns; David D Moore Journal: Nat Commun Date: 2016-02-18 Impact factor: 14.919