An atypical case of inherited Creutzfeldt–Jakob disease (CJD) is described in a 35-year-old Dutch woman, homozygous for methionine at codon 129 of the prion protein gene (PRNP). The clinical phenotype was characterised by slowly progressive cognitive decline and parkinsonism. Neuropathological findings consisted of scanty spongiosis and only faint to absent immunohistochemical staining for the abnormal prion protein, PrPSc, with patchy deposits in the cerebellar cortex. Purkinje cells were abnormally located in the molecular layer of the cerebellum. Western blot analysis showed the co-occurrence of PrPSc types 1 and 2 with an unusual distribution. Sequence analysis disclosed a novel 120 bp insertion in the octapeptide repeat region of the PRNP, encoding five additional R2 octapeptide repeats. These features define an unusual neuropathological phenotype and novel genotype, further expanding the spectrum of genotype–phenotype correlations in inherited prion diseases and emphasising the need to carry out pre-mortem PRNP sequencing in all young patients with atypical dementias.
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See Editorial Commentary, p 1303
Funding Supported in part by a governmental grant: RIVM Antonie van Leeuwenhoeklaan, 93721 MA Bilthoven, The Netherlands.
Competing interests None.
Provenance and Peer review Not commissioned; externally peer reviewed.