BACKGROUND: Between January 1993 and December 2003, 19 @entity1 with @entity1579 due to the @entity50407 mutation were referred to the regional epidemiological registry for spongiform @entity75 in the Basque Country in Spain, a small community of some 2,100,000 inhabitants. METHODS: Ten further @entity1 belonging to the same pedigrees were retrospectively ascertained through neurological or neuropathological records. In four of the @entity1 , the diagnosis was confirmed by analysing DNA obtained from paraffin blocks. In this article, we report on the clinical, genetic, and pathological features of the 23 @entity1 carrying the @entity50407 mutation confirmed by genetic molecular analysis. Haplotyping studies suggest a founder effect among Basque born families, explaining in part this unusually high incidence of the @entity50407 mutation in a small community. Only two @entity1 (8%) lack familial antecedents. RESULTS: We have observed a phenotypic variability even among homozygous 129MM @entity1 . Our findings challenge the currently accepted belief that MM homozygosity in codon 129 is always related to a @entity14749 ( @entity14749 ) phenotype. Indeed, seven out of 17 @entity1 with a 129MM genotype in this series presented with a @entity3605 ( @entity3605 ) clinicopathological picture. CONCLUSIONS: The considerable clinical and pathological overlapping observed among homozygous 129MM @entity1 favours the view that @entity14749 and CJD178 are the extremes of a spectrum rather than two discrete and separate entities. Other genetic or environmental factors apart from the polymorphism in codon 129 may play a role in determining the phenotypic expression of the @entity50407 mutation in the @entity3669 gene.

Phenotypic variability in XXXX due to the @entity50407 mutation.

@entity1 :: ('9606', 'Species') :: ['patients'] @entity50407 :: ('p|SUB|D|178|N', 'ProteinMutation') :: ['D178N'] @entity75 :: ('MESH:D001927', 'Disease') :: ['encephalopathies'] @entity1579 :: ('MESH:D017096', 'Disease') :: ['familial prion diseases'] @entity3605 :: ('MESH:D007562', 'Disease') :: ['Creutzfeldt-Jakob disease', 'CJD'] @entity3669 :: ('5621', 'Gene') :: ['PRNP'] @entity14749 :: ('MESH:D034062', 'Disease') :: ['fatal familial insomnia', 'FFI']
@entity1579 :: (MESH:D017096,Disease) :: ['familial prion diseases']
