New ATP7B Gene Mutation in a Brazilian Patient with Wilson Disease
  • Marcus Villander Barros de Oliveira Sá
    Real Clínica Médica; Real Hospital Português de Beneficência em Pernambuco, Recife, Brazil; Instituto Aggeu Magalhães – Fundação Oswaldo Cruz, Recife, Brazil
  • Flavio José Siqueira Pacheco
    Real Clínica Médica; Real Hospital Português de Beneficência em Pernambuco, Recife, Brazil
  • Jorge Luiz Carvalho Figueredo
    Real Clínica Médica; Real Hospital Português de Beneficência em Pernambuco, Recife, Brazil
  • Gustavo Henrique de Sá Miranda Cavancante Filho
    Real Clínica Médica; Real Hospital Português de Beneficência em Pernambuco, Recife, Brazil
  • Thiago de Oliveira Silva
    Real Clínica Médica; Real Hospital Português de Beneficência em Pernambuco, Recife, Brazil
  • Luydson Richardson Vasconcelos Silva
    Instituto Aggeu Magalhães – Fundação Oswaldo Cruz, Recife, Brazil

Keywords

Wilson disease, ATP7B gene, older age

Abstract

We report the case of a 70-year-old man diagnosed with late-onset Wilson disease (WD) with mild neurological symptoms only and a new mutation in the ATP7B gene. A compound mutation of the ATP7B gene was found with the variant c.98T>C p(Met33Thr) in exon 2, in heterozygosis, and variant c.2224G>A (Val742Ile) in exon 8, in heterozygosis. Patient age should not be a determinant for excluding WD. Genetic sequencing is an important tool for the discovery of new genetic mutations.

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References

  • Takiyama Y, Nishizawa M, Tanaka H, Kawashima S, Sakamoto H, Karube Y, et al. The gene for Machado-Joseph disease maps to human chromosome 14q. Nat Genet 1993;4:300–304.
  • Terada K, Schilsky ML, Miura N, Sugiyama T. ATP7B (WND) protein. Int J Biochem Cell Biol 1998;30:1063–1067.
  • Bull PC, Cox DW. Wilson disease and Menkes disease: new handles on heavy-metal transport. Trends Genet 1994;10:246–252.
  • 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;3:1647–1656.
  • Riordan SM, Williams R. The Wilson’s disease gene and phenotypic diversity. J Hepatol 2001;34:165–171.
  • Gomes A, Dedoussis GV. Geographic distribution of ATP7B mutations in Wilson disease. Ann Hum Biol 2016;43:1–8.
  • Ferenci P, Czlonkowska A, Stremmel W, Houwen R, Rosenberg W, Schilsky M, et al. EASL Clinical Practice Guidelines: Wilson’s disease. J Hepatol 2012;56:671–685.
  • Kulkarni A, Sharma VK. Wilson’s disease. Int Encycl Public Heal 2016;6:424–433.
  • Czlonkowska A, Rodo M, Gromadzka G. Late onset Wilson’s disease: therapeutic implications. Mov Disord 2008;23:897–899.
  • Ala A, Borjigin J, Rochwarger A, Schilsky M. Wilson disease in septuagenarian siblings: raising the bar for diagnosis. Hepatology 2005;41:668–670.
  • Thomas GR, Forbes JR, Roberts EA, Walshe JM, Cox DW. The Wilson disease gene: spectrum of mutations and their consequences. Nat Genet 1995;9:210–217.
  • 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;20:112–117.
  • Lee BH, Kim JH, Lee SY, Jin HY, Kim KJ, Lee JJ, et al. Distinct clinical courses according to presenting phenotypes and their correlations to ATP7B mutations in a large Wilson’s disease cohort.Liver Int 2011;31:833–841.
  • Kieffer DA, Medici V. Wilson disease: at the crossroads between genetics and epigenetics—a review of the evidence. Liver Res 2017;1:121–130.
  • Deguti MM, Genschel J, Cancado ELR, Barbosa ER, Bochow B, Mucenic M, et al. Wilson disease: novel mutations in the ATP7B gene and clinical correlation in Brazilian patients. Hum Mutat 2004;23:398.
  • Bem RS de, Raskin S, Muzzillo DA, Deguti MM, Cançado ELR, Araújo TF, et al. Wilson’s disease in Southern Brazil: genotype-phenotype correlation and description of two novel mutations in ATP7B gene. Arq Neuropsiquiatr 2013;71:503–507.
  • Wilson DC, Phillips MJ, Cox DW, Roberts EA. Severe hepatic Wilson’s disease in preschool-aged children. J Pediatr 2000;137:719–722.
  • Ferenci P, Czlonkowska A, Merle U, Ferenc S, Gromadzka G, Yurdaydin C, et al. Late-onset Wilson’s disease. Gastroenterology 2007;132:1294–1298.
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    Published: 2022-12-01
    Issue: 2022: Vol 9 No 12 (view)


    How to cite:
    1.
    Villander Barros de Oliveira Sá M, Siqueira Pacheco FJ, Carvalho Figueredo JL, de Sá Miranda Cavancante Filho GH, de Oliveira Silva T, Vasconcelos Silva LR. New ATP7B Gene Mutation in a Brazilian Patient with Wilson Disease. EJCRIM 2022;9 doi:10.12890/2022_003655.