ABCB11 gene mutations in Chinese children with progressive intrahepatic cholestasis and low γ glutamyltransferase

Liver International

Volumn 30, Issue 6, 2010, Pages 809-815

  Liu, Li Yan ^a,b   Wang, Zhong Lin ^a,b   Wang, Xiao Hong ^a,b   Zhu, Qi Rong ^a,b   Wang, Jian She ^a,b  

^a CHILDREN S HOSPITAL OF FUDAN UNIVERSITY   (China)

^b FUDAN UNIVERSITY   (China)

Author keywords

ABCB11 gene; Bile salt export protein; Low GGT; Mutation; Progressive intrahepatic cholestasis

Indexed keywords

CARRIER PROTEIN; GAMMA GLUTAMYLTRANSFERASE; ABC TRANSPORTER; ABCB11 PROTEIN, HUMAN; STOP CODON;

ABCB11 GENE; ARTICLE; CHINESE; CLINICAL ARTICLE; FEMALE; FRAMESHIFT MUTATION; GAMMA GLUTAMYL TRANSFERASE BLOOD LEVEL; GENE; HISTOPATHOLOGY; HUMAN; INFANT; INTRAHEPATIC CHOLESTASIS; MALE; MISSENSE MUTATION; NEWBORN; NONSENSE MUTATION; NUCLEOTIDE SEQUENCE; PROGRESSIVE FAMILIAL INTRAHEPATIC CHOLESTASIS TYPE 2; ALTERNATIVE RNA SPLICING; ASIAN CONTINENTAL ANCESTRY GROUP; CHILD; CHINA; DEFICIENCY; ENZYMOLOGY; EPIDEMIOLOGY; ETHNOLOGY; EXON; GENETIC PREDISPOSITION; GENETICS; HOSPITAL; INTRON; LIVER; METABOLISM; MUTATION; NEEDLE BIOPSY; PATHOLOGY; PHENOTYPE; PRESCHOOL CHILD; STOP CODON;

ALTERNATIVE SPLICING; ASIAN CONTINENTAL ANCESTRY GROUP; ATP-BINDING CASSETTE TRANSPORTERS; BIOPSY, NEEDLE; CHILD; CHILD, PRESCHOOL; CHINA; CHOLESTASIS, INTRAHEPATIC; CODON, NONSENSE; EXONS; FEMALE; GAMMA-GLUTAMYLTRANSFERASE; GENETIC PREDISPOSITION TO DISEASE; HOSPITALS, PEDIATRIC; HUMANS; INFANT; INTRONS; LIVER; MALE; MUTATION; MUTATION, MISSENSE; PHENOTYPE;

EID: 77954368755     PISSN: 14783223     EISSN: 14783231     Source Type: Journal    
DOI: 10.1111/j.1478-3231.2009.02112.x     Document Type: Article

References (28)

1. Danks DM, Campbell PE, Jack I, Rogers J, Smith AL. Studies of the aetiology of neonatal hepatitis and biliary atresia. Arch Dis Child 1977, 52:360-7.
2. Dick MC, Mowat AP. Hepatitis syndrome in infancy: an epidemiologic survey with 10-year follow up. Arch Dis Child 1985, 60:512-6.
3. Cavestro GM, Frulloni L, Cerati E. Progressive familial intrahepatic cholestasis. Acta Biomed 2002, 73:53-6.
4. Strautnieks SS, Kagalwalla AF, Tanner MS. Identification of a locus for progressive familial intrahepatic cholestasis PFIC2 on chromosome 2q24. Am J Hum Genet 1997, 61:630-3.
5. Strautnieks SS, Bull LN, Knisely AS. A gene encoding a liver-specific ABC transporter is mutated in progressive familial intrahepatic cholestasis. Nat Genet 1998, 20:233-8.
6. Byrne JA, Strautnieks SS, Mieli-Vergani G. The human bile salt export pump: characterization of substrate specificity and identification of inhibitors. Gastroenterology 2002, 123:1659-66.
7. Jansen PL, Strautnieks SS, Jacquemin E. Hepatocanalicular bile salt export pump deficiency in patients with progressive familial intrahepatic cholestasis. Gastroenterology 1999, 117:1370-9.
8. Bull LN, van Eijk MJ, Pawlikowska L. A gene encoding a P-type ATPase mutated in two forms of hereditary cholestasis. Nat Genet 1998, 18:219-24.
9. Chen HL, Chang PS, Hsu HC. FIC1 and BSEP defects in Taiwanese patients with chronic intrahepatic cholestasis with low γ-glutamyltranspeptidase levels. J Pediatr 2002, 140:119-24.
10. Chen HL, Liu YJ, Su YN. Diagnosis of BSEP/ABCB11 mutations in Asian patients with cholestasis using denaturing high performance liquid chromatography. J Pediatr 2008, 153:825-32.
11. Wang JS, Wang ZL, Wang XH. The prognostic value of serum gamma glutamyltransferase activity in Chinese infants with previously diagnosed idiopathic neonatal hepatitis. HK J Paediatri (New Series) 2008, 13:39-45.
12. Lang T, Haberl M, Jung D. Genetic variability, haplotype structures, and ethnic diversity of hepatic transporters MDR3 (ABCB4) and bile salt export pump (ABCB11). Drug Metab Dispos 2006, 34:1582-99.
13. http://genes.mit.edu/burgelab/maxent/Xmaxentscan_scoreseq, Available at
14. Eng L, Coutinho G, Nahas S. Nonclassical splicing mutations in the coding and noncoding regions of the ATM gene: maximum entropy estimates of splice junction strengths. Hum Mutat 2004, 23:67-76.
15. Cartegni L, Wang J, Zhu Z, Zhang MQ, Krainer AR. ESEfinder: a web resource to identify exonic splicing enhancers. Nucleic Acids Res 2003, 31:3568-71.
16. Smith PJ, Zhang C, Wang J. An increased specificity score matrix for the prediction of SF2/ASF-specific exonic splicing enhancers. Hum Mol Genet 2006, 15:2490-508.
17. Reese MG. http://fruitfly.org/seq_tools/splice.html, Splice site prediction by neural network. Available at
18. Reese MG, Eeckman FH, Kulp D, Haussler D. Improved splice site detection in Genie. J Comput Biol 1997, 4:311-23.
19. Byrne JA, Strautnieks SS, Ihrke G. Missense mutations and single nucleotide polymorphisms in ABCB11 impair bile salt export pump processing and function or disrupt pre-messenger RNA splicing. Hepatology 2009, 49:553-67.
20. Linton KJ. Structure and function of ABC transporters. Physiology 2007, 22:122-30.
21. Kerr ID, Berridge G, Linton KJ. Definition of the domain boundaries is critical to the expression of the nucleotide-binding domains of P-glycoprotein. Eur Biophys J 2003, 32:644-54.
22. Goto K, Sugiyama K, Sugiura T. Bile salt pump gene mutations in two Japanese patients with progressive familial intrahepatic cholestasis. J Pediatr Gastroenterol Nutr 2003, 36:647-50.
23. Strautnieks SS, Byrne JA, Pawlikowska L. Severe bile salt export pump deficiency: 82 different ABCB11 mutations in 109 families. Gastroenterology 2008, 134:1203-14.
24. Walkowiak J, Jankowska I, Pawlowska J. Exocrine pancreatic function in children with progressive familial intrahepatic cholestasis type 2. J Pediatr Gastroenterol Nutr 2006, 24:416-8.
25. Knisely AS, Strautnieks SS, Meier Y. Hepatocellular carcinoma in ten children under five years of age with bile salt export pump deficiency. Hepatology 2006, 44:478-86.
26. Scheimann AO, Strautnieks SS, Knisely AS. Mutations in bile salt export pump (ABCB11) in two children with progressive familial intrahepatic cholestasis and cholangiocarcinoma. J Pediatr 2007, 150:556-9.
27. Wang L, Soroka CJ, Boyer JL. The role of bile salt export pump mutations in progressive familial intrahepatic cholestasis type II. J Clin Invest 2002, 110:965-72.
28. Bull LN, van Eijk MJ, Pawlikowska L. A gene encoding a P-type ATPase mutated in two forms of hereditary cholestasis. Nat Genet 1998, 18:219-24.