Inherited Creutzfeldt-Jakob disease in a British family associated with a novel 144 base pair insertion of the prion protein gene.

Abstract

A case of familial Creutzfeldt-Jakob disease associated with a 144 base pair insertion in the-open reading frame of the prion protein gene is described. Sequencing of the mutated allele showed an arrangement of-six octapeptide repeats, distinct from that of a recently described British family with an insertion of similar size. Thirteen years previously the brother of the proband had died from "Huntington's disease", but re-examination of his neuropathology revealed spongiform encephalopathy and antiprion protein immunocytochemistry gave a positive result. The independent evolution of at least two distinct pathological 144 base pair insertions in Britain is proposed. The importance of maintaming a high index of suspicion of inherited Creutzfeldt-Jakob disease in cases of familial neurodegenerative disease is stressed. (J Neurol Neurosurg Psychiatry 1995;58:65-69)

Two mutant prion proteins expressed in cultured cells acquire biochemical properties reminiscent of the scrapie isoform.

“…1). PG11 moPrP contains six octapeptide repeats in addition to the normal five, and its human homologue has been described in a large English pedigree spanning seven generations (21-23) and, more recently, in two other families (24,25). E199K moPrP carries a Glu -> Lys substitution at codon 199, and its human homologue (E200K) has been identified in several families of Libyan-born Jews (26,27), as well as in families originating in a number of other countries (27)(28)(29).…”

Context dependent neuroprotective properties of prion protein (PrP)

“…Some cases of diagnosed HD are actually caused by a mutation in the gene encoding PrP (PRNP) rather than any alteration to the huntingtin gene. 44,45 PRNP mutations can also be associated with some PD-like symptoms and neuropathology 46 and some demonstrate similarities to the tauopathies. 47 Collinge and colleagues described a kindred segregating pre-senile dementia, AD, HD, PD, Pick's disease, as well as prion disease (GerstmannStraussler-Scheinker syndrome and CJD).…”

Rapidly progressive dementia syndrome associated with a novel four extra repeat mutation in the prion protein gene

“…1 2 The insertional mutations described so far consist of one to nine (but not three) extra octapeptide repeats, between codons 51 and 91 of the PrP gene. [3][4][5][6][7][8][9][10][11][12][13][14][15][16] This region normally comprises one nonapeptide (R1) followed by four octapeptides (R2, R2, R3, R4), which have the same amino acid sequence but can be distinguished by variations in DNA sequence. Reports of five to nine extra octapeptide repeats indicate an autosomal dominant pattern of inheritance and a considerably heterogeneous phenotype of prion diseases.…”

“…Reports of five to nine extra octapeptide repeats indicate an autosomal dominant pattern of inheritance and a considerably heterogeneous phenotype of prion diseases. [8][9][10][11][12][13][14][15][16] Conversely, small octapeptide insertions of one, two, or four extra repeats usually present as classic Creutzfeldt-Jakob disease (CJD). Patients with these types of mutation usually lack a family history of neurological disorders.…”