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. 1997 Sep;61(3):630–633. doi: 10.1086/515501

Identification of a locus for progressive familial intrahepatic cholestasis PFIC2 on chromosome 2q24.

S S Strautnieks 1, A F Kagalwalla 1, M S Tanner 1, A S Knisely 1, L Bull 1, N Freimer 1, S A Kocoshis 1, R M Gardiner 1, R J Thompson 1
PMCID: PMC1715942  PMID: 9326328

Abstract

Progressive familial intrahepatic cholestasis (PFIC; OMIM 211600) is the second most common familial cholestatic syndrome presenting in infancy. A locus has previously been mapped to chromosome 18q21-22 in the original Byler pedigree. This chromosomal region also harbors the locus for benign recurrent intrahepatic cholestasis (BRIC) a related phenotype. Linkage analysis in six consanguineous PFIC pedigrees from the Middle East has previously excluded linkage to chromosome 18q21-22, indicating the existence of locus heterogeneity within the PFIC phenotype. By use of homozygosity mapping and a genome scan in these pedigrees, a locus designated "PFIC2" has been mapped to chromosome 2q24. A maximum LOD score of 8.5 was obtained in the interval between marker loci D2S306 and D2S124, with all families linked.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adler M., Chung K. W., Schaffner F. Pericanalicular hepatocytic and bile ductular microfilaments in cholestasis in man. Am J Pathol. 1980 Mar;98(3):603–616. [PMC free article] [PubMed] [Google Scholar]
  2. Bull L. N., Carlton V. E., Stricker N. L., Baharloo S., DeYoung J. A., Freimer N. B., Magid M. S., Kahn E., Markowitz J., DiCarlo F. J. Genetic and morphological findings in progressive familial intrahepatic cholestasis (Byler disease [PFIC-1] and Byler syndrome): evidence for heterogeneity. Hepatology. 1997 Jul;26(1):155–164. doi: 10.1002/hep.510260121. [DOI] [PubMed] [Google Scholar]
  3. Carlton V. E., Knisely A. S., Freimer N. B. Mapping of a locus for progressive familial intrahepatic cholestasis (Byler disease) to 18q21-q22, the benign recurrent intrahepatic cholestasis region. Hum Mol Genet. 1995 Jun;4(6):1049–1053. doi: 10.1093/hmg/4.6.1049. [DOI] [PubMed] [Google Scholar]
  4. Collins A., Frezal J., Teague J., Morton N. E. A metric map of humans: 23,500 loci in 850 bands. Proc Natl Acad Sci U S A. 1996 Dec 10;93(25):14771–14775. doi: 10.1073/pnas.93.25.14771. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dib C., Fauré S., Fizames C., Samson D., Drouot N., Vignal A., Millasseau P., Marc S., Hazan J., Seboun E. A comprehensive genetic map of the human genome based on 5,264 microsatellites. Nature. 1996 Mar 14;380(6570):152–154. doi: 10.1038/380152a0. [DOI] [PubMed] [Google Scholar]
  6. Frimmer M., Ziegler K. The transport of bile acids in liver cells. Biochim Biophys Acta. 1988 Feb 24;947(1):75–99. doi: 10.1016/0304-4157(88)90020-2. [DOI] [PubMed] [Google Scholar]
  7. Hagenbuch B., Stieger B., Foguet M., Lübbert H., Meier P. J. Functional expression cloning and characterization of the hepatocyte Na+/bile acid cotransport system. Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10629–10633. doi: 10.1073/pnas.88.23.10629. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Houwen R. H., Baharloo S., Blankenship K., Raeymaekers P., Juyn J., Sandkuijl L. A., Freimer N. B. Genome screening by searching for shared segments: mapping a gene for benign recurrent intrahepatic cholestasis. Nat Genet. 1994 Dec;8(4):380–386. doi: 10.1038/ng1294-380. [DOI] [PubMed] [Google Scholar]
  9. Inoue M., Kinne R., Tran T., Arias I. M. Taurocholate transport by rat liver canalicular membrane vesicles. Evidence for the presence of an Na+-independent transport system. J Clin Invest. 1984 Mar;73(3):659–663. doi: 10.1172/JCI111257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kagalwalla A. F., Al Amir A. R., Khalifa A., Sylven M., Al Ajaji S., Kagalwalla Y. A. Progressive familial intrahepatic cholestasis (Byler's disease) in Arab children. Ann Trop Paediatr. 1995 Dec;15(4):321–327. doi: 10.1080/02724936.1995.11747792. [DOI] [PubMed] [Google Scholar]
  11. Kruglyak L., Daly M. J., Reeve-Daly M. P., Lander E. S. Parametric and nonparametric linkage analysis: a unified multipoint approach. Am J Hum Genet. 1996 Jun;58(6):1347–1363. [PMC free article] [PubMed] [Google Scholar]
  12. Strautnieks S. S., Kagalwalla A. F., Tanner M. S., Gardiner R. M., Thompson R. J. Locus heterogeneity in progressive familial intrahepatic cholestasis. J Med Genet. 1996 Oct;33(10):833–836. doi: 10.1136/jmg.33.10.833. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Weber A. M., Tuchweber B., Yousef I., Brochu P., Turgeon C., Gabbiani G., Morin C. L., Roy C. C. Severe familial cholestasis in North American Indian children: a clinical model of microfilament dysfunction? Gastroenterology. 1981 Oct;81(4):653–662. [PubMed] [Google Scholar]
  14. Whitington P. F., Freese D. K., Alonso E. M., Schwarzenberg S. J., Sharp H. L. Clinical and biochemical findings in progressive familial intrahepatic cholestasis. J Pediatr Gastroenterol Nutr. 1994 Feb;18(2):134–141. doi: 10.1097/00005176-199402000-00003. [DOI] [PubMed] [Google Scholar]
  15. Wong M. H., Rao P. N., Pettenati M. J., Dawson P. A. Localization of the ileal sodium-bile acid cotransporter gene (SLC10A2) to human chromosome 13q33. Genomics. 1996 May 1;33(3):538–540. doi: 10.1006/geno.1996.0233. [DOI] [PubMed] [Google Scholar]

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