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2016, Number 3

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Biotecnol Apl 2016; 33 (3)

Study of T991T polymorphism in Cuban patients with clinical diagnosis of Wilson’s disease

Clark Y, Ruenes C, García EF, Collazo T, Roblejo H, Morales E, Robaina Z

Language: English
References: 19
Page: 3221-3224
PDF size: 290.05 Kb.


ABSTRACT

Wilson’s disease is characterized by the accumulation of copper mainly in the liver. It is transmitted with an autosomal recessive inheritance pattern. The molecular cause is mutations in the atp7b gene, which is found on chromosome 13. Several polymorphisms in the atp7b gene have been reported in the literature. To identify the T991T polymorphism in Cuban patients clinically diagnosed with Wilson’s disease, a descriptive study was conducted at the Centro Nacional de Genética Médica during the 2008-2012 period including 100 patients. For the amplification of the fragment of interest, the Polymerase Chain Reaction (PCR) technique was used and the PCR-amplified DNA product of exon 13 from the atp7b gene was analyzed by Single Stranded Conformational Polymorphism (SSCP) technique to identify the conformational shifts. The presence of the T991T polymorphism was identified by sequencing the analyzed DNA fragment. Two different conformational shift were detected: a, corresponding to the normal gene alleles variant; and b, corresponding to the T991T polymorphism in heterozygous state. The allelic frequency of the T991T polymorphism in the 100 Cuban patients clinically diagnosed with Wilson’s disease was found to be 9.5 %. These findings provide a characterization of this Wilson’s disease polymorphism in the Cuban population and it will make possible to conduct molecular studies by indirect methods.


REFERENCES

  1. Kumar SS, Kurian G, Eapen CE, Roberts EA. Genetics of Wilson’s disease: a clinical perspective. Indian J Gastroenterol. 2012;31(6):285-93.

  2. Kenney SM, Cox DW. Sequence variation database for the Wilson disease copper transporter, ATP7B. Hum Mutat. 2007;28(12):1171-7.

  3. Badenas Orquin C. Advances in the molecular diagnosis of Wilson’s disease. Gastroenterol Hepatol. 2011;34(6): 428-33.

  4. Li XH, Lu Y, Ling Y, Fu QC, Xu J, Zang GQ, et al. Clinical and molecular characterization of Wilson’s disease in China: identification of 14 novel mutations. BMC Med Genet. 2011;12:6.

  5. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988;16(3):1215.

  6. WMA Declaration of Helsinki - Ethical Principles for Medical Research Involving Human Subjects [Internet]. Ferney-Voltaire: World Medical Association, Inc.; 2013 [cited 2016 Oct 11]. Available from: http://www.wma.net/ en/30publications/10policies/b3/.

  7. Margarit E, Bach V, Gomez D, Bruguera M, Jara P, Queralt R, et al. 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.

  8. Cox DW, Prat L, Walshe JM, Heathcote J, Gaffney D. Twenty-four novel mutations in Wilson disease patients of predominantly European ancestry. Hum Mutat. 2005;26(3):280.

  9. Zali N, Mohebbi SR, Esteghamat S, Chiani M, Haghighi MM, Hosseini-Asl SM, et al. Prevalence of ATP7B Gene Mutations in Iranian Patients With Wilson Disease. Hepat Mon. 2011;11(11):890-4.

  10. Simsek Papur O, Akman SA, Cakmur R, Terzioglu O. Mutation analysis of ATP7B gene in Turkish Wilson disease patients: identification of five novel mutations. Eur J Med Genet. 2013;56(4):175-9.

  11. Simsek Papur O, Asik Akman S, Terzioglu O. Clinical and genetic analysis of pediatric patients with Wilson disease. Turk J Gastroenterol. 2015;26(5):397-403.

  12. Clark Y, Collazo T, Ruenes C, García E, Robaina Z, Fragoso T, et al. Detección de cambios conformacionales y mutaciones en el exón 8 del gen ATP7B en pacientes cubanos con la enfermedad de Wilson. Biotecnol Apl. 2011;28(2):87-90.

  13. Clark Y, Collazo T, Ruenes C, García EF, Robaina Z, Fragoso T. Análisis molecular del exón 2 del gen ATP7B en pacientes cubanos con la enfermedad de Wilson. Rev Habanera Cienc Méd. 2011;10(3):281-6.

  14. Ljubic H, Kalauz M, Telarovic S, Ferenci P, Ostojic R, Noli MC, et al. ATP7B Gene Mutations in Croatian Patients with Wilson Disease. Genet Test Mol Biomarkers. 2016;20(3):112-7.

  15. Aggarwal A, Chandhok G, Todorov T, Parekh S, Tilve S, Zibert A, et al. Wilson disease mutation pattern with genotypephenotype correlations from Western India: confirmation of p.C271* as a common Indian mutation and identification of 14 novel mutations. Ann Hum Genet. 2013;77(4): 299-307.

  16. Paradisi I, De Freitas L, Arias S. Most frequent mutation c.3402delC(p.Ala1135GlnfsX13) among Wilson disease patients in Venezuela has a wide distribution and two old origins. Eur J Med Genet. 2015;58(2):59-65.

  17. Curtis D, Durkie M, Balac P, Sheard D, Goodeve A, Peake I, et al. A study of Wilson disease mutations in Britain. Hum Mutat. 1999;14(4):304-11.

  18. Wu F, Wang J, Pu C, Qiao L, Jiang C. Wilson’s disease: a comprehensive review of the molecular mechanisms. Int J Mol Sci. 2015;16(3):6419-31.

  19. Clark Y, Ruenes C, García EF, Collazo T, Robaina Z, Castañeda C, et al. Identificación del polimorfismo K832R en pacientes con diagnóstico clínico de la enfermedad de Wilson. Rev Habanera Cienc Méd. 2013;12(2): 197-202.




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