title: Phenotypic variability in fatal familial insomnia (D178N-129M) genotype.
abstract: OBJECTIVE
  To report the clinical and pathologic features of patients with the D178N-129M mutation living in Germany.
  
  
  METHODS
  Patients with clinically suspected Creutzfeldt-Jakob disease (CJD) were seen in an ongoing, prospective epidemiologic study from June 1993 to August 1997 throughout Germany. Suspect patients were referred to the CJD unit by the participating hospitals or physicians. Patients were seen by a physician, and each patient underwent a detailed neurologic examination. Prion protein gene (PRNP) analysis was performed to distinguish patients with familial forms of CJD.
  
  
  RESULTS
  The constellation D178N-129M was identified in eight individuals; in one patient, the diagnosis was made by neuropathologic examination. Four affected men and five women belong to eight unrelated families. A family history of a neurodegenerative disorder was recalled in only five patients. In contrast to the first reported fatal familial insomnia (FFI) patient, none of our patients complained of severe, untreatable insomnia in the early stages. Dysautonomia was observed in varying degrees in most patients. The clinical course of these patients resembled sporadic CJD. In six patients, brain tissue was available for neuropathologic study. In one patient, the neuropathologic examination showed changes that were more reminiscent of forms of sporadic CJD; in the remaining five, the histopathology was typical of FFI.
  
  
  CONCLUSIONS
  The clinical presentation in patients with FFI may vary to a great extent. Genotyping of the patients was crucial in providing laboratory confirmation of the diagnosis of FFI, even when there was no family history of a prion disease.
authors.affiliation: Neurologische Klinik, Georg-August-Universität Göttingen, Germany.
authors.forename: I
authors.initials: I
authors.lastname: Zerr
authors.forename: A
authors.initials: A
authors.lastname: Giese
authors.forename: O
authors.initials: O
authors.lastname: Windl
authors.forename: S
authors.initials: S
authors.lastname: Kropp
authors.forename: W
authors.initials: W
authors.lastname: Schulz-Schaeffer
authors.forename: C
authors.initials: C
authors.lastname: Riedemann
authors.forename: K
authors.initials: K
authors.lastname: Skworc
authors.forename: M
authors.initials: M
authors.lastname: Bodemer
authors.forename: H A
authors.initials: HA
authors.lastname: Kretzschmar
authors.forename: S
authors.initials: S
authors.lastname: Poser
mesh_terms: D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D007562:Creutzfeldt-Jakob Syndrome / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D005858:Germany / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D017096:Prion Diseases / Q000453:epidemiology* / Q000235:genetics*; D011328:Prions / Q000235:genetics*; D015183:Restriction Mapping
chemical_list: D011328:Prions