A cluster of familial Creutzfeldt-Jakob disease mutations recapitulate conserved residues in Doppel: a case of molecular mimicry?

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Abstract
Intrachromosomal deletions linking Dpl expression to the PrP promoter produce cerebellar degeneration that can be abrogated by the introduction of wild‐type PrP transgenes. Since Dpl‐like truncated forms of PrP are neuropathogenic in mice and likewise counterbalanced by expression of PrPC we asked whether naturally occurring mutant forms of human PrP have Dpl‐like attributes. Five PRNP missense mutations causing familial Creutzfeldt–Jakob disease (F‐CJD) map to a helical region found in both PrPC and Dpl and result in amino acids identical to conserved residues in Dpl. These F‐CJD alleles may cause mutant PrP to become a weak mimetic of Dpl structure and/or function.