Novel twelve-generation kindred of fatal familial insomnia from Germany representing the entire spectrum of disease expression

Autor: Anja Harder, Jens P. Dreier, Otto Windl, Torsten Wirth, Karsten Lohan, Regine Witkowski, Friedmar Kreuz, Nadja Karnatz, Klaus Jendroska, Constanze Schafranka, Hans A. Kretzschmar, Jorge Cervós-Navarro, Aguta Théallier‐Janko, Dirk Emmerich, Peter Nürnberg
Rok vydání: 1999
Předmět:
Zdroj: American Journal of Medical Genetics. 87:311-316
ISSN: 1096-8628
0148-7299
DOI: 10.1002/(sici)1096-8628(19991203)87:4<311::aid-ajmg6>3.0.co;2-5
Popis: We present a novel large German kindred of fatal familial insomnia (FFI) consisting of three branches and comprising more than 800 individuals of 12 generations, the largest pedigree of any familial prion disease known today. There is a wide spectrum of clinical presentations leading to misdiagnoses of Olivo-Ponto-Cerebellar Atrophy (OPCA), Parkinson's or Alzheimer's disease in addition to Creutzfeldt-Jakob disease (CJD) and Gerstmann-Straussler-Scheinker (GSS) syndrome. Molecular genetic analysis of the prion protein gene (PRNP) confirmed the mutation D178N segregating with methionine at the polymorphic codon 129 of PRNP in all 7 patients examined. This polymorphism at codon 129 is supposed to discriminate between familial CJD (fCJD) and FFI; the 129M allele determines FFI and 129V fCJD. Furthermore, heterozygosity at this site appears to induce prolonged disease duration as compared to the homozygous condition. The variability of the clinical and pathological findings documented for our patients indicates the difficulty in establishing the diagnosis of FFI on clinical and on pathological grounds alone. In three cases (IX-97, XI-21, V-2) followed up by us prospectively insomnia was an early and severe symptom; however, in case notes analyzed retrospectively this symptom was frequently missed. In contrast to previous reports and in agreement with recent studies we cannot confirm a clear relationship between the status of the M/V polymorphism at codon 129 and the age-of-onset of this disease.
Databáze: OpenAIRE
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