High phenotypic variability in Gerstmann-Sträussler-Scheinker disease

Jerusa Smid; Adalberto Studart Neto; Michele Christine Landemberger; Cleiton Fagundes Machado; Paulo Ribeiro Nóbrega; Nathalie Henriques Silva Canedo; Rodrigo Rizek Schultz; Michel Satya Naslavsky; Sérgio Rosemberg; Fernando Kok; Leila Chimelli; Vilma Regina Martins; Ricardo Nitrini

doi:10.1590/0004-282X20170049

Arquivos de Neuro-Psiquiatria, Inhaltsverzeichnis

CC BY-NC-ND 4.0 · Arq Neuropsiquiatr 2017; 75(06): 331-338
DOI: 10.1590/0004-282X20170049

ARTICLE

High phenotypic variability in Gerstmann-Sträussler-Scheinker disease

Elevada variabilidade fenotípica na doença de Gerstmann-Sträussler-Scheinker

Jerusa Smid

¹Universidade de São Paulo, Faculdade de Medicina, Departamento de Neurologia, São Paulo SP, Brasil;

,

Adalberto Studart Neto

¹Universidade de São Paulo, Faculdade de Medicina, Departamento de Neurologia, São Paulo SP, Brasil;

,

Michele Christine Landemberger

²A. C. Camargo Cancer Center, São Paulo SP, Brasil;

,

Cleiton Fagundes Machado

²A. C. Camargo Cancer Center, São Paulo SP, Brasil;

,

Paulo Ribeiro Nóbrega

³Universidade Federal do Ceará, Faculdade de Medicina, Departamento de Neurologia, Fortaleza CE Brasil;

,

Nathalie Henriques Silva Canedo

⁴Universidade Federal do Rio de Janeiro, Departamento de Patologia, Rio de Janeiro RJ, Brasil;

,

Rodrigo Rizek Schultz

⁵Universidade Federal de São Paulo, Seção de Neurologia Comportamental, São Paulo SP, Brasil;

,

Michel Satya Naslavsky

⁶Universidade de São Paulo, Instituto de Biociências, Centro de Estudos do Genoma Humano, São Paulo SP, Brasil;

,

Sérgio Rosemberg

⁷Universidade de São Paulo, Departamento de Patologia, Divisão de Neuropatologia, São Paulo SP, Brasil.

,

Fernando Kok

¹Universidade de São Paulo, Faculdade de Medicina, Departamento de Neurologia, São Paulo SP, Brasil;

,

Leila Chimelli

⁴Universidade Federal do Rio de Janeiro, Departamento de Patologia, Rio de Janeiro RJ, Brasil;

,

Vilma Regina Martins

²A. C. Camargo Cancer Center, São Paulo SP, Brasil;

,

Ricardo Nitrini

¹Universidade de São Paulo, Faculdade de Medicina, Departamento de Neurologia, São Paulo SP, Brasil;

› Institutsangaben

Abstract

ABSTRACT

Gerstmann-Sträussler-Scheinker is a genetic prion disease and the most common mutation is p.Pro102Leu. We report clinical, molecular and neuropathological data of seven individuals, belonging to two unrelated Brazilian kindreds, carrying the p.Pro102Leu. Marked differences among patients were observed regarding age at onset, disease duration and clinical presentation. In the first kindred, two patients had rapidly progressive dementia and three exhibited predominantly ataxic phenotypes with variable ages of onset and disease duration. In this family, age at disease onset in the mother and daughter differed by 39 years. In the second kindred, different phenotypes were also reported and earlier ages of onset were associated with 129 heterozygosis. No differences were associated with apoE genotype. In these kindreds, the codon 129 polymorphism could not explain the clinical variability and 129 heterozygosis was associated with earlier disease onset. Neuropathological examination in two patients confirmed the presence of typical plaques and PrP^sc immunopositivity.

RESUMO

A doença de Gerstmann-Sträussler-Scheinker é uma doença priçnica genética, cuja mutação mais frequente é p.Pro102Leu. Descrevem-se dados clínicos, moleculares e neuropatológicos de sete indivíduos em duas famílias não relacionadas com p.Pro102Leu. Diferenças notáveis entre os pacientes em relação à idade de início, duração da doença e apresentação clínica foram encontradas. Na primeira família, dois pacientes apresentaram demência rapidamente progressiva e três apresentaram fenótipo de ataxia com idade variáveis de início e duração da doença. Nesta família, a idade de início entre mãe e filha diferiu em 39 anos. Na segunda família, fenótipos diferentes foram observados e idades precoces de início dos sintomas foram associadas à heterozigose no códon 129. Não houve diferença em relação ao genótipo do gene da apoE. O genótipo do códon 129 não foi responsável pela variabilidade clínica; heterozigose no códon 129 esteve associada ao início precoce da doença. O exame neuropatológico em dois pacientes confirmou presença de placas típicas e imunohistoquímica para PrPsc.

Gerstmann-Sträussler-Scheinker disease - prion diseases - prions

doença de Gerstmann-Sträussler-Scheinker - doenças de prion - príons

Volltext

Referenzen

References
1 Prusiner SB. Prions. Proc Natl Acad Sci USA. 1998;95(23):13363-83. https://doi.org/10.1073/pnas.95.23.13363
2 Holman RC, Belay ED, Christensen KY, Maddox RA, Minino AM, Folkema AM et al. Human prion diseases in the United States. PLoS One;2010;5(1):e8521. https://doi.org/10.1371/journal.pone.0008521
3 Puoti G, Bizzi A, Forloni G, Safar JG, Tagliavini F, Gambetti P. Sporadic human prion diseases: molecular insights and diagnosis. Lancet Neurol. 2012;11(7):618-28. https://doi.org/10.1016/S1474-4422(12)70063-7
4 Wadsworth JD, Hill AF, Beck JA, Collinge J. Molecular and clinical classification of human prion disease. Br Med Bull. 2003;66(1):241-54. https://doi.org/10.1093/bmb/66.1.241
5 Ladogana A, Puopolo M, Croes EA, Budka H, Jarius C, Collins S et al. Mortality from Creutzfeldt-Jakob disease and related disorders in Europe, Australia, and Canada. Neurology. 2005;64(9):1586-91. https://doi.org/10.1212/01.WNL.0000160117.56690.B2
6 Gerstmann J, Straussler E, Scheinker J. Über eine eigenartige hereditär-familiäre Erkrankung des Zentralnervensystems. Z Neurol. 1936;154:736-62.
7 Hsiao K, Baker HF, Crow TJ, Poulter M, Owen F, Terwilliger JD et al. Linkage of a prion protein missense variant to Gerstmann-Sträussler syndrome. Nature. 1989;338(6213):342-5. https://doi.org/10.1038/338342a0
8 Kretzschmar HA, Honold G, Seitelberger F, Feucht M, Wessely P, Mehraein P et al. Prion protein mutation in family first reported by Gerstmann, Sträussler and Scheinker. Lancet. 1991;337(8750):1160. https://doi.org/10.1016/0140-6736(91)92826-N
9 Collins S, McLean CA, Masters CL. Gerstmann-Sträussler-Scheinker syndrome, fatal familial insomnia, and kuru: a review of these less common human transmissible spongiform encephalopathies. J Clin Neurosci. 2001;8(5):387-97. https://doi.org/10.1054/jocn.2001.0919
10 Arata H, Takashima H, Hirano R, Tomimitsu H, Machigashira K, Izumi K et al. Early clinical signs and imaging findings in Gerstmann-Sträussler-Scheinker syndrome (Pro102Leu). Neurology. 2006;66(11):1672-8. https://doi.org/10.1212/01.wnl.0000218211.85675.18
11 Hainfellner JA, Brantner-Inthaler S, Cervenáková L, Brown P, Kitamoto T, Tateishi J et al. The original Gerstmann-Sträussler-Scheinker family of Austria: divergent clinicopathological phenotypes but constant PrP genotype. Brain Pathol. 1995;5(3):201-11. https://doi.org/10.1111/j.1750-3639.1995.tb00596.x
12 Piccardo P, Dlouhy SR, Lievens PM, Young K, Bird TD, Nochlin D et al. Phenotypic variability of Gerstmann-Sträussler-Scheinker disease is associated with prion protein heterogeneity. J Neuropathol Exp Neurol. 1998;57(10):979-88. https://doi.org/10.1097/00005072-199810000-00010
13 Riudavets MA, Sraka MA, Schultz M, Rojas E, Martinetto H, Begué C et al. Gerstmann-Sträussler-Scheinker syndrome with variable phenotype in a new kindred with PRNP-P102L mutation. Brain Pathol. 2014;24(2):142-7. https://doi.org/10.1111/bpa.12083
14 Webb TE, Poulter M, Beck J, Uphill J, Adamson G, Campbell T et al. Phenotypic heterogeneity and genetic modification of P102L inherited prion disease in an international series. Brain. 2008;131(10):2632-46. https://doi.org/10.1093/brain/awn202
15 Mead S. Prion disease genetics. Eur J Hum Genet. 2006;14(3):273-81. https://doi.org/10.1038/sj.ejhg.5201544
16 Wadsworth JD, Joiner S, Linehan JM, Cooper S, Powell C, Mallinson G et al. Phenotypic heterogeneity in inherited prion disease (P102L) is associated with differential propagation of protease-resistant wild-type and mutant prion protein. Brain. 2006;129(6):1557-69. https://doi.org/10.1093/brain/awl076
17 Castro RM, Landemberger MC, Walz R, Carlotti CG Jr, Huang N, Cunha DR et al. High capacity and low cost detection of prion protein gene variant alleles by denaturing HPLC. J Neurosci Methods. 2004;139(2):263-9. https://doi.org/10.1016/j.jneumeth.2004.05.001
18 Calero O, Hortigüela R, Bullido MJ, Calero M. Apolipoprotein E genotyping method by real time PCR, a fast and cost-effective alternative to the TaqMan and FRET assays. J Neurosci Methods. 2009;183(2):238-40. https://doi.org/10.1016/j.jneumeth.2009.06.033
19 Doh-ura K, Tateishi J, Sasaki H, Kitamoto T, Sakaki Y. Pro→Leu change at position 102 of prion protein is the most common but not the sole mutation related to Gerstmann-Sträussler-Scheinker syndrome. Biochem Biophys Res Commun. 1989;163(2):974-9. https://doi.org/10.1016/0006-291X(89)92317-6
20 Kovács GG, Puopolo M, Ladogana A, Pocchiari M, Budka H, Duijn C et al. Genetic prion disease: the EUROCJD experience. Hum Genet. 2005;118(2):166-74. https://doi.org/10.1007/s00439-005-0020-1
21 Barbanti P, Fabbrini G, Salvatore M, Petraroli R, Cardone F, Maras B et al. Polymorphism at codon 129 or codon 219 of PRNP and clinical heterogeneity in a previously unreported family with Gerstmann-Sträussler-Scheinker disease (PrP-P102L mutation). Neurology. 1996;47(3):734-41. https://doi.org/10.1212/WNL.47.3.734
22 Majtényi C, Brown P, Cervenáková L, Goldfarb LG, Tateishi J. A three-sister sibship of Gerstmann-Sträussler-Scheinker disease with a CJD phenotype. Neurology. 2000;54(11):2133-7. https://doi.org/10.1212/WNL.54.11.2133
23 Ishizawa K, Komori T, Shimazu T, Yamamoto T, Kitamoto T, Shimazu K et al. Hyperphosphorylated tau deposition parallels prion protein burden in a case of Gerstmann-Sträussler-Scheinker syndrome P102L mutation complicated with dementia. Acta Neuropathol. 2002;104(4):342-30. https://doi.org/10.1007/s00401-002-0547-3
24 Giovagnoli AR, Di Fede G, Aresi A, Reati F, Rossi G, Tagliavini F. Atypical frontotemporal dementia as a new clinical phenotype of Gerstmann-Straussler-Scheinker disease with the PrP-P102L mutation: description of a previously unreported Italian family. Neurol Sci. 2008;29(6):405-10. https://doi.org/10.1007/s10072-008-1025-z
25 Calero O, Bullido MJ, Clarimón J, Frank-García A, Martínez-Martín P, Lleó A et al. Genetic cross-interaction between APOE and PRNP in sporadic Alzheimer’s and Creutzfeldt-Jakob diseases. PLoS One. 2011;6(7):e22090. https://doi.org/10.1371/journal.pone.0022090
26 Chapman J, Cervenáková L, Petersen RB, Lee HS, Estupinan J, Richardson S et al. APOE in non-Alzheimer amyloidoses: transmissible spongiform encephalopathies. Neurology. 1998;51(2):548-53. https://doi.org/10.1212/WNL.51.2.548
27 Ellison D, Love S, Chimelli L et al. Neuropathology: a reference text of CNS pathology. 3rd ed. Lonson: Elsevier-Mosby; 2013.
28 Jansen C, Head MW, Rozemuller AJ, Ironside JW. Panencephalopathic Creutzfeldt-Jakob disease in the Netherlands and the UK: clinical and pathological characteristics of nine patients. Neuropathol Appl Neurobiol. 2009;35(3):272-82. https://doi.org/10.1111/j.1365-2990.2008.01004a.x
29 Iwasaki Y, Mori K, Ito M, Nokura K, Tatsumi S, Mimuro M et al. Gerstmann-Straeussler-Scheinker disease with P102L prion protein gene mutation presenting with rapidly progressive clinical course. Clin Neuropathol. 2014;33(5):344-53. https://doi.org/10.5414/NP300733
30 Minikel EV, Zerr I, Collins SJ, Ponto C, Boyd A, Klug G et al. Ascertainment bias causes false signal of anticipation in genetic prion disease. Am J Hum Genet. 2014;95(4):371-82. https://doi.org/10.1016/j.ajhg.2014.09.003
31 Chi NF, Lee YC, Lu YC, Wu HM, Soong BW. Transmissible spongiform encephalopathies with P102L mutation of PRNP manifesting different phenotypes: clinical, neuroimaging, and electrophysiological studies in Chinese kindred in Taiwan. J Neurol. 2010;257(2):191-7. https://doi.org/10.1007/s00415-009-5290-4
32 Irisawa M, Amanuma M, Kozawa E, Kimura F, Araki N. A case of Gerstmann-Sträussler-Scheinker syndrome. Magn Reson Med Sci. 2007;6(1):53-7. https://doi.org/10.2463/mrms.6.53