title: Diagnosis of BSEP/ABCB11 mutations in Asian patients with cholestasis using denaturing high performance liquid chromatography.
abstract: OBJECTIVE
  To determine if specific mutations were present in Asian patients with progressive familial intrahepatic cholestasis (PFIC) type 2 caused by defects in bile salt export pump (BSEP), encoded by ABCB11.
  
  
  METHODS
  A combination of denaturing high-performance liquid chromatography (DHPLC) and direct sequencing was used to screen ABCB11 mutations in 18 Taiwanese patients with low gamma-glutamyltransferase PFIC or benign recurrent intrahepatic cholestasis (BRIC). Polymorphisms were also analyzed in patients with PFIC (n = 21), neonatal cholestasis (n = 23), and control subjects (n = 88).
  
  
  RESULTS
  Seven mutations in 4 of 16 patients with PFIC from different families were detected by DHPLC, including M183V, V284L, R303K, R487H, W493X, G1004D, and 1145delC. G1004D was found in a patient with BRIC. L827I was found in another patient with neonatal cholestasis. Absent or defective BSEP staining was found in the liver of patients with mutations. Polymorphisms V444A and A865V, with an allele frequencies 75.6% and 0.6%, respectively, were found in our population. No differences were found between patients with cholestasis and control subjects.
  
  
  CONCLUSIONS
  One-fourth of Taiwanese patients with PFIC/BRIC had compound heterozygous or single heterozygous ABCB11 mutations without hot spots. All of the mutations were different from those detected in Western countries.
authors.affiliation: Department of Pediatrics, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan.
authors.forename: Huey-Ling
authors.initials: HL
authors.lastname: Chen
authors.forename: Yu-Jung
authors.initials: YJ
authors.lastname: Liu
authors.forename: Yi-Ning
authors.initials: YN
authors.lastname: Su
authors.forename: Nai-Yu
authors.initials: NY
authors.lastname: Wang
authors.forename: Shang-Hsin
authors.initials: SH
authors.lastname: Wu
authors.forename: Yen-Hsuan
authors.initials: YH
authors.lastname: Ni
authors.forename: Hong-Yuan
authors.initials: HY
authors.lastname: Hsu
authors.forename: Tzee-Chung
authors.initials: TC
authors.lastname: Wu
authors.forename: Mei-Hwei
authors.initials: MH
authors.lastname: Chang
mesh_terms: D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D002780:Cholestasis, Intrahepatic / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics*; D002851:Chromatography, High Pressure Liquid; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation / Q000235:genetics*; D011110:Polymorphism, Genetic; D013624:Taiwan
chemical_list: C093491:ABCB11 protein, human; D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters