Novel twelve-generation kindred of fatal familial insomnia from Germany representing the entire spectrum of disease expression
- 3 December 1999
- journal article
- case report
- Published by Wiley in American Journal of Medical Genetics
- Vol. 87 (4) , 311-316
- https://doi.org/10.1002/(sici)1096-8628(19991203)87:4<311::aid-ajmg6>3.0.co;2-5
Abstract
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‐Sträussler‐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. Am. J. Med. Genet. 87:311–316, 1999.Keywords
This publication has 24 references indexed in Scilit:
- SeqHelp: A Program to Analyze Molecular Sequences Utilizing Common Computational ResourcesGenome Research, 1998
- Fatal insomnia in a case of familial Creutzfeldt-Jakob disease with the codon 200 Lys mutationNeurology, 1996
- Fatal Familial Insomnia and Familial Creutzfeldt‐Jakob Disease: Clinical, Pathological and Molecular FeaturesBrain Pathology, 1995
- Codon 178 mutation of the human prion protein gene in a German family (Backer family): sequencing data from 72-year-old celloidin-embedded brain tissueActa Neuropathologica, 1995
- Novel Missense Variants of Prion Protein in Creutzfeldt-Jakob Disease or Gerstmann-Sträussler SyndromeBiochemical and Biophysical Research Communications, 1993
- Fatal Familial Insomnia and Familial Creutzfeldt-Jakob Disease: Disease Phenotype Determined by a DNA PolymorphismScience, 1992
- A PrP gene codon 178 base substitution and a 24‐bp interstitial deletion in familial Creutzfeldt‐Jakob diseaseNeurology, 1992
- Mutant prion proteins in Gerstmann-Sträussler-Scheinker disease with neurofibrillary tanglesNature Genetics, 1992
- Creutzfeldt‐Jakob disease cosegregates with the codon 178AsnPRNP mutation in families of European originAnnals of Neurology, 1992
- Molecular Cloning of a Human Prion Protein cDNADNA, 1986