Fatal Familial Insomnia (FFI) is a hereditary prion disease caused by a mutation at codon 178 of the prion-protein gene leading to a D178N substitution in the protein determining severe and selective atrophy of mediodorsal and anteroventral thalamic nuclei.
Additionally, increased YKL-40 levels were found in genetic prion diseases associated with the PRNP-D178N (Fatal Familial Insomnia) and PRNP-E200K mutations.
Fatal familial insomnia (FFI) linked to a D178N/129M haplotype mutation in the PRNP gene is the most common genetic prion disease in the Han Chinese population.
Fatal familial insomnia is a rare disease caused by a D178N mutation in combination with methionine (Met) at codon 129 in the mutated allele of PRNP (D178N-129M haplotype).
We report here a Chinese case of FFI with a D178N/Met129 genotype of the PRNP gene, who exhibited rapidly progressive dementia combined with behavioral disturbances and paroxysmal limb myoclonus.
Typically, the D178N mutation associated with the 129M genotype is related to fatal familial insomnia while the same mutation associated with the 129V genotype is linked to familial CJD.
Collectively, these observations suggest that methionine oxidation accelerates the aggregation and enhances the neurotoxicity of the D178N variant, possibly providing direct evidence to link the pathogenesis of D178N-associated FFI with methionine oxidation.
These findings underline the clear-cut distinction between the neuropathological features of Creutzfeldt-Jakob disease associated with D178N PRNP mutation and those of fatal familial insomnia.
Fatal familial insomnia (FFI) is a special subtype of genetic human prion diseases that is caused by the D178N mutation of the prion protein gene (PRNP).
We characterize SSOs in a 51-year-old male with FFI carrying the D178N mutation and the methionine/methionine homozygosity at the polymorphic 129 codon of the PRNP gene and in eight gender and age-matched healthy controls.
Fatal familial insomnia (FFI) and genetic Creutzfeldt-Jakob disease (CJD(D178N,)(129V)) are two phenotypes that share a common point mutation at codon 178 of the prion protein gene (PRNP), but differ in their polymorphism at codon 129 of the mutant allele.
Recent phenotype-genotype correlation studies revealed a considerable clinical and pathological overlap for patients with the D178N mutation, suggesting a continuous spectrum between fatal familial insomnia and Creutzfeldt-Jakob Disease phenotype.
Genotyping of SNPs in conjunction with the analysis of genealogical data for a group of FFI patients revealed the existence of two distinct haplotypes potentially associated with the D178N mutation.
One such mutation (Asp178 --> Asn) is associated with two distinct disorders: fatal familial insomnia or familial Creutzfeldt-Jakob disease, depending upon the presence of Met or Val at position 129, respectively.
Twelve apparently unrelated FFI and fCJD pedigrees with the characteristic D178N mutation have been reported in the Prion Diseases Registry of the Basque Country since 1993.
The authors present clinical, sleep, and neuroendocrine features of a patient with genetically confirmed fatal familial insomnia (D178N mutation with heterozygosity at codon 129 of the prion protein gene).
Accumulation of an isoform of protease-resistant PrP fragment in FFI distinct from that found in a familial form of Creutzfeldt-Jakob disease with the same D178N mutation, shows the effect of the polymorphism at codon 129 of PRNP on phenotypic expression and the possibility of distinct prion "strains" with diverse pathological potential.