Common Polymorphisms of ATP7B Gene as a Good Marker in Linkage Analysis in Wilson Disease Patients from Southern Iran

Document Type : Original Articles

Authors

1 Department of Medical Genetics, Shiraz University of Medical Sciences, Shiraz, Iran

2 Shiraz Transplant Research Center, Gastroenterohepatology Research Center, Namazi Teaching Hospital, Shiraz University of Medical Sciences, Shiraz, Iran

3 Department of Internal Medicine, Gastroenterology and Hepatology Research Center, Shiraz U

4 Department of Medical Genetics, Shiraz University of Medical Sciences, Shiraz; Stem Cell and Transgenic Technology Research Center, Shiraz University of Medical Sciences, Shiraz, IR Iran; Department of Molecular Medicine, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran

Abstract

Background: Wilson disease (WD) is caused by numerous pathogenic mutations of the ATP7B gene. There are several mutation screening methods that can be used for the diagnosis and carrier detection of WD, however such methods are costly and time-consuming. Therefore, other diagnostic methods should be used for urgent situations such as prenatal diagnosis. Objective: To report common polymorphisms of ATP7B gene in WD patients from southern Iran to be use in linkage analysis in the WD affected families. Material and methods: Genomic DNA was extracted from 30 patients and PCR was carried out for ATP7B gene. DHPLC was then performed and PCR products with abnormal peak profiles were subjected to direct DNA sequencing. Result: Several patients showed abnormal peak profiles in DHPLC analysis and subsequent sequencing results demonstrated that some polymorphisms were more common in southern Iran. Those were c.1216T>G (exon 2), c.1366C>G (exon 3), c.3419 T>C (exon 16), c.3903 + 6C>T (intron 18) and c.4021+50G>C (intron 19). Conclusion: These common polymorphisms can be used by linkage analysis for the prenatal diagnosis and carrier detection in affected families with Wilson disease.

Keywords

References

  1. Frommer D, Morris J, Sherlock S, Abrams J, Newman S. Kayser-Fleischer-like rings in patients without Wilson's disease. Gastroenterology. 1977; 72(6):1331-5. PubMed PMID: 558126.
  2. Ferenci P. Regional distribution of mutations of the ATP7B gene in patients with Wilson disease: impact on genetic testing. Hum Genet 2006; 120(2):151-9.
  3. Compston A. Progressive lenticular degeneration: a familial nervous disease associated with cirrhosis of the liver, by S. A. Kinnier Wilson, (From the National Hospital, and the Laboratory of the National Hospital, Queen Square, London) Brain 1912: 34; 295-509. Brain. 2009; 132 (Pt 8):1997-2001. Epub 2009/07/28.
  4. Steindl P, Ferenci P, Dienes HP, Grimm G, Pabinger I, Madl C, Maier-Dobersberger T, Herneth A, Dragosics B, Meryn S, Knoflach P, Granditsch G, Gangl A. Wilson's disease in patients presenting with liver disease: a diagnostic challenge. Gastroenterology 1997; 113(1):212-8. Epub 1997/07/01.
  5. Cauza E, Maier-Dobersberger T, Polli C, Kaserer K, Kramer L, Ferenci P. Screening for Wilson's disease in patients with liver diseases by serum ceruloplasmin. J Hepatol 1997; 27(2):358-62. Epub 1997/08/01.
  6. Merle U, Schaefer M, Ferenci P, Stremmel W. Clinical presentation, diagnosis and long-term outcome of Wilson's disease: a cohort study. Gut 2007; 56(1):115-20. Epub 2006/05/20.
  7. Underhill PA, Jin L, Lin AA, Mehdi SQ, Jenkins T, Vollrath D, Davis RW, Cavalli-Sforza LL, Oefner PJ. Detection of numerous Y chromosome biallelic polymorphisms by denaturing high-performance liquid chromatography. Genome Res1997; 7(10):996-1005. Epub 1997/10/23.
  8. Guida V, Colosimo A, Fiorito M, Foglietta E, Bianco I, Ivaldi G, Fichera M, Dallapiccola B. Denaturing HPLC-based assay for molecular screening of nondeletional mutations causing alpha-thalassemias. Clin Chem 2004; 50(7):1242-5. Epub 2004/07/02.
  9. Lin D, Goldstein JA, Mhatre AN, Lustig LR, Pfister M, Lalwani AK. Assessment of denaturing high-performance liquid chromatography (DHPLC) in screening for mutations in connexin 26 (GJB2). Hum Mutat 2001; 18(1):42-51. Epub 2001/07/05.
  10. van Den Bosch BJ, de Coo RF, Scholte HR, Nijland JG, van Den Bogaard R, de Visser M, de Die-Smulders CE, Smeets HJ. Mutation analysis of the entire mitochondrial genome using denaturing high performance liquid chromatography. Nucleic Acids Res 2000; 28(20):E89. Epub 2000/10/12.
  11. Kuklin A, Munson K, Gjerde D, Haefele R, Taylor P. Detection of single-nucleotide polymorphisms with the WAVE DNA fragment analysis system. Genet Test 1997; 1(3):201-6. Epub 1997/01/01.
  12. Larsen LA, Christiansen M, Vuust J, Andersen PS. Recent developments in high-throughput mutation screening. Pharmacogenomics 2001; 2(4):387-99. Epub 2001/11/28.
  13. Wagner T, Stoppa-Lyonnet D, Fleischmann E, Muhr D, Pages S, Sandberg T, Caux V, Moeslinger R, Langbauer G, Borg A, Oefner P. Denaturing high-performance liquid chromatography detects reliably BRCA1 and BRCA2 mutations. Genomics 1999; 62(3):369-76. Epub 2000/01/25.
  14. Yu B, Sawyer NA, Chiu C, Oefner PJ, Underhill PA. DNA mutation detection using denaturing high-performance liquid chromatography (DHPLC). Curr Protoc Hum Genet 2006; Chapter 7:Unit7 10. Epub 2008/04/23.
  15. Loudianos G, Lovicu M, Dessi V, Tzetis M, Kanavakis E, Zancan L, Zelante L, Galvez-Galvez C, Cao A. Abnormal mRNA splicing resulting from consensus sequence splicing mutations of ATP7B. Hum Mutat 2002; 20(4):260-6. Epub 2002/09/27.
  16. Farrer LA, Bowcock AM, Hebert JM, Bonne-Tamir B, Sternlieb I, Giagheddu M, St George-Hyslop P, Frydman M, Lossner J, Demelia L, et al. Predictive testing for Wilson's disease using tightly linked and flanking DNA markers. Neurology 1991; 41(7):992-9. Epub 1991/07/01.
  17. Petrukhin K, Lutsenko S, Chernov I, Ross BM, Kaplan JH, Gilliam TC. Characterization of the Wilson disease gene encoding a P-type copper transporting ATPase: genomic organization, alternative splicing, and structure/function predictions. Hum Mol Genet 1994; 3(9):1647-56. Epub 1994/09/01.
  18. Terada K, Nakako T, Yang XL, Iida M, Aiba N, Minamiya Y, Nakai M, Sakaki T, Miura N, Sugiyama T. Restoration of holoceruloplasmin synthesis in LEC rat after infusion of recombinant adenovirus bearing WND cDNA. J Biol Chem 1998; 273(3):1815-20. Epub 1998/01/27.
  19. Terada K, Aiba N, Yang XL, Iida M, Nakai M, Miura N, Sugiyama T. Biliary excretion of copper in LEC rat after introduction of copper transporting P-type ATPase, ATP7B. FEBS Lett 1999; 448(1):53-6. Epub 1999/04/27.
  20. Sternlieb I, Van den Hamer CJ, Morell AG, Alpert S, Gregoriadis G, Scheinberg IH. Lysosomal defect of hepatic copper excretion in Wilson's disease (hepatolenticular degeneration). Gastroenterology 1973; 64(1):99-105. Epub 1973/01/01.
  21. Zali N, Mohebbi SR, Esteghamat S, Chiani M, Haghighi MM, Hosseini-Asl SM, Derakhshan F, Mohammad-Alizadeh AH, Malek-Hosseini SA, Zali MR. Prevalence of ATP7B Gene Mutations in Iranian Patients With Wilson Disease. Hepat Mon 2011; 11(11):890-4. Epub 2012/02/07.
  22. Margarit E, Bach V, Gomez D, Bruguera M, Jara P, Queralt R, Ballesta F. Mutation analysis of Wilson disease in the Spanish population -- identification of a prevalent substitution and eight novel mutations in the ATP7B gene. Clin Genet 2005; 68(1):61-8. Epub 2005/06/15.
  23. Davies LP, Macintyre G, Cox DW. New mutations in the Wilson disease gene, ATP7B: implications for molecular testing. Genet Test. 2008; 12(1):139-45. Epub 2008/04/01. doi: 10.1089/gte.2007.0072. PubMed PMID: 18373411.
  24. Abdelghaffar TY, Elsayed SM, Elsobky E, Bochow B, Buttner J, Schmidt H. Mutational analysis of ATP7B gene in Egyptian children with Wilson disease: 12 novel mutations. J Hum Genet 2008; 53(8):681-7. Epub 2008/05/17.
  25. Gromadzka G, Schmidt HH, Genschel J, Bochow B, Rodo M, Tarnacka B, Litwin T, Chabik G, Czlonkowska A. Frameshift and nonsense mutations in the gene for ATPase7B are associated with severe impairment of copper metabolism and with an early clinical manifestation of Wilson's disease. Clin Genet 2005; 68(6):524-32. Epub 2005/11/15.
  26. Maier-Dobersberger T, Ferenci P, Polli C, Balac P, Dienes HP, Kaserer K, Datz C, Vogel W, Gangl A. Detection of the His1069Gln mutation in Wilson disease by rapid polymerase chain reaction. Ann Intern Med 1997; 127(1):21-6. Epub 1997/07/01.
  27. Caca K, Ferenci P, Kuhn HJ, Polli C, Willgerodt H, Kunath B, Hermann W, Mossner J, Berr F. High prevalence of the H1069Q mutation in East German patients with Wilson disease: rapid detection of mutations by limited sequencing and phenotype-genotype analysis. J Hepatol 2001; 35(5):575-81. Epub 2001/11/03.
  28. Firneisz G, Lakatos PL, Szalay F, Polli C, Glant TT, Ferenci P. Common mutations of ATP7B in Wilson disease patients from Hungary. Am J Med Genet 2002; 108(1):23-8. Epub 2002/02/22.
  29. Panagiotakaki E, Tzetis M, Manolaki N, Loudianos G, Papatheodorou A, Manesis E, Nousia-Arvanitakis S, Syriopoulou V, Kanavakis E. Genotype-phenotype correlations for a wide spectrum of mutations in the Wilson disease gene (ATP7B). Am J Med Genet A 2004; 131(2):168-73. Epub 2004/11/04.
  30. Panichareon B, Taweechue K, Thongnoppakhun W, Aksornworanart M, Pithukpakorn M, Yenchitsomanus PT, Limwongse C, Limjindaporn T. Six novel ATP7B mutations in Thai patients with Wilson disease. Eur J Med Genet 2011; 54(2):103-7. Epub 2010/11/03.
  31. Schollen E, Dequeker E, McQuaid S, Vankeirsbilck B, Michils G, Harvey J, van den Akker E, van Schooten R, Clark Z, Schrooten S, Matthijs G. Diagnostic DHPLC Quality Assurance (DDQA): a collaborative approach to the generation of validated and standardized methods for DHPLC-based mutation screening in clinical genetics laboratories. Hum Mutat 2005; 25(6):583-92. Epub 2005/05/10.
  32. Dierick HA, Ambrosini L, Spencer J, Glover TW, Mercer JF. Molecular structure of the Menkes disease gene (ATP7A). Genomics 1995; 28(3):462-9.
  33. Lao O, van Duijn K, Kersbergen P, de Knijff P, Kayser M. Proportioning whole-genome single-nucleotide-polymorphism diversity for the identification of geographic population structure and genetic ancestry. American journal of human genetics 2006; 7 8(4):680-90.
  34. Kao SL, Chong SS, Lee CG. The role of single nucleotide polymorphisms (SNPs) in understanding complex disorders and pharmacogenomics. Annals of the Academy of Medicine, Singapore 2000; 29(3):376-82.
  35. Bodmer WF. Genetic diversity and disease susceptibility. Philosophical transactions of the Royal Society of London Series B, Biological sciences. 1997; 352(1357):1045-50. doi: 10.1098/rstb.1997.0083. PubMed PMID: 9304669; PubMed Central PMCID: PMC1691996.
  36. Elahi E, Kumm J, Ronaghi M. Global genetic analysis. Journal of biochemistry and molecular biology 2004; 37(1):11-27.
Journal of Advanced Medical Sciences and Applied Technologies
Volume 1, Issue 1 - Serial Number 1
4
September 2015
Pages 30-34

Files

Share

How to cite

Statistics