Creutzfeldt-Jakob disease associated with a missense mutation at codon 200 of the prion protein gene in Brazil

Doença de Creutzfeldt-Jakob associada com mutação de ponto no códon 200 do gene da proteína príon no Brasil

Abstract

Genetic Creutzfeldt-Jakob disease (gCJD) represents less than 15% of CJD cases, and its clinical picture may be either indistinguishable from that of sporadic CJD (sCJD) or be atypical, usually with younger onset and longer duration. We report a case of 59-year old Brazilian man who presented rapidly progressive cognitive decline and cerebellar ataxia. EEG revealed periodic activity. A brother and a cousin of the patient had CJD. A point mutation at codon 200 (E200K) of the prion protein gene (PRNP) was found and death occurred 11 months after onset of symptoms. Autopsy was not performed. The clinical presentation of gCJD associated with E200K, which is the most frequent PRNP mutation, is quite similar to sCDJ. This is the first report of E200K mutation in Brazil, and it is possible that a more systematic search for its occurrence may show it to be relatively frequent in Brazil.

Key words:
prion; genetic Creutzfeldt-Jakob disease; E200K.

Resumo

A forma genética da doença de Creutzfeldt-Jakob (gDCJ) representa aproximadamente 15% dos casos de DCJ e o quadro clínico pode ser indistinguível do observado na forma esporádica (eDCJ) ou pode ser atípico, geralmente com início precoce e maior sobrevida. Relatamos o caso de paciente do sexo masculino, 59 anos, que apresentou declínio cognitivo rapidamente progressivo associado a ataxia cerebelar. EEG revelou atividade periódica. DCJ havia sido diagnosticada no irmão e prima do paciente. A avaliação genética evidenciou mutação de ponto no códon 200 (E200K). Óbito ocorreu 11 meses após o início dos sintomas. Não foi realizada autópsia. O quadro clínico da gDCJ associada a E200K é semelhante ao da eDCJ, sendo esta a mutação mais freqüente no gene da proteína prion (PRNP). Este é o primeiro relato da mutação E200K no Brasil, e é possível que a pesquisa rotineira de mutações no PRNP possa identificar maior freqüência desta mutação em nosso meio.

Palavras-chave:
príon; doença de Creutzfeldt-Jakob; forma genética; E200K.

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References

• ¹
  Prusiner SB. Molecular biology of prion diseases. Science 1991;252:1515-1522.
• ²
  Masters CL, Gajdusek DC, Gibbs CJ. The familial occurrence of Creutzfeldt-Jakob disease and Alzheimer's disease. Brain 1981;104:535-558.
• ³
  Prusiner SB, Hsiao KK.. Human prion diseases. Ann Neurol 1994;35:385-395.
• ⁴
  Kong Q, Surewicz WK, Petersen RB et al. Inherited prion diseases. In: Prusiner SD, editor. Prion Biology and Diseases. 2nd ed. Cold Spring Harbor: Cold Spring Harbor Laboratory Press; 2004:673-775.
• ⁵
  Knight SG, Will RG. Prion diseases. J Neurol Neurosurg Psychiatry 2004;75(Suppl I):i36-i42.
• ⁶
  Lee HS, Sambuughin N, Cervenakova L et al. Ancestral origins and worldwide distribution of the PRNP 200K mutation causing familial Creutzfeldt-Jakob disease. Am J Hum Genet 1999;64:1063-1107.
• ⁷
  Brown P, Galvez S, Goldfarb LG et al. Familial Creutzfeldt-Jakob disease in Chile is associated with the codon 200 mutation of the PRNP amyloid precursor gene on chromosome 20. J Neurol Sci 1992;112:65-67.
• ⁸
  Ladogana A, Puopolo M, Poleggi A et al. High incidence of genetic human transmissible spongiform encephalopathies in Italy. Neurology 2005;64:1592-1597.
• ⁹
  Mitrova E, Belay G. Creutzfeldt-Jakob disease with E200K mutation in Slovakia: characterization and development. Acta Virol 2002;46:31-39.
• ¹⁰
  Kovacs GG, Majtenyi K. Creutzfeldt-Jakob disease in Hungary. Folia Neuropathol 2005;43:279-285.
• ¹¹
  Meiner Z, Gabizon R, Prusiner SB. Familial Creutzfeldt-Jakob disease. Codon 200 prion disease in Libyan Jews. Medicine (Baltimore) 1997 ;76:227-237.
• ¹²
  Hsiao K, Meiner Z, Kahana E et al. Mutation of the prion protein in Libyan Jews with Creutzfeldt-Jakob disease. N Engl J Med 1991;324:1091-1097.
• ¹³
  Mitrova E, Belay G. Creutzfeldt-Jakob disease with E200K mutation in Slovakia: characterization and development. Acta Virol 2002;46:31-39.
• ¹⁴
  Caboclo LO, Huang N, Lepski GA et al. Iatrogenic Creutzfeldt-Jakob disease following human growth hormone therapy: case report. Arq Neuropsiquiatr 2002;60:458-461.
• ¹⁵
  Macario ME, Vaisman M, Buescu A, et al. Pituitary growth hormone and Creutzfeldt-Jakob disease. Br Med J 1991; 302:1149.
• ¹⁶
  Nitrini R, Rosemberg S, Passos-Bueno MR et al. Familial spongiform encephalopathy associated with a novel prion protein gene mutation. Ann Neurol 1997;42:138-146.
• ¹⁷
  Huang N, Marie SK, Kok F, Nitrini R. Familial Creutzfeldt-Jakob disease associated with a point mutation at codon 210 of prion protein gene. Arq Neuropsiquiatr 2001;59:932-935.
• ¹⁸
  Brown P, Cathala F, Castaigne P, Gajdusek DC. Creutzfeldt-Jakob disease: Clinical analysis of a consecutive series of 230 neuropathologically verified cases. Ann Neurol 1986;20:597-602.
• ¹⁹
  Brown P, Goldfarb LG, Gibbs CJ Jr, Gajdusek DC. The phenotypic expression of different mutations in transmissible familial Creutzfeldt-Jakob disease. Eur J Epidemiol 1991;7:469-476.
• ²⁰
  Kahana E, Zilber N, Abraham M. Do Creutzfeldt-Jakob disease patients of Jewish Libyan origin have unique clinical features? Neurology 1991;41:1390-1392.
• ²¹
  Chapman J, Ben-Israel J, Goldhammer Y, Korczyn AD. The risk of developing Creutzfeldt-Jakob disease in subjects with the PRNP gene codon 200 point mutation. Neurology 1994;44:1683-1686.
• ²²
  Spudich S, Mastrianni JA, Wrensch M et al. Complete penetrance of Creutzfeldt-Jakob disease in Libyan Jews carrying the E200K mutation in the prion protein gene. Mol Med 1995;1:607-613.
• ²³
  WHO recommended surveillance standards, 2nd edition. WHO, Geneva, pp.35-38.
• ²⁴
  Kovacs GG, Puopolo M, Ladogana A et al. Genetic prion disease: the EUROCJD experience. Hum Genet 2005;118:166-174.

Publication Dates

• Publication in this collection
  Apr-Jun 2007