Inherited prion disease with 4-octapeptide repeat insertion linked to valine at codon 129

Abstract

Sir, We have read the article by Kaski et al. (2011) with great interest, where the authors describe the results of their investigations of patients from the UK with four extra octapeptide repeat insertions (OPRIs) in the prion protein gene ( PRNP) . Herein, we would like to present a case that we had the opportunity to study with four extra OPRIs in the PRNP gene, but associated with a different genetic background at codon 129. Kaski et al . (2011) analysed 10 patients with four extra OPRIs. The predominant clinical syndrome was a rapidly progressive cortical dementia with myoclonus, motor and cerebellar signs resembling sporadic Creutzfeldt-Jakob disease (CJD). Age at onset and disease duration presented considerable variability; the mean age of onset was 60 years (range 39–85 years) with median disease duration of 414 days (range 59–2319 days). The 14-3-3 test was positive in all tested patients ( n = 4). MRI showed hyperintensities typical of sporadic CJD only in one out of five patients studied. The genetic analysis revealed that all patients have additional four R2 repeats within the repetitive part of the PRNP gene located between positions 51 and 91, and all of them were homozygous for methionine (M) at codon 129. Only one patient presented with familial history of early-onset dementia suggesting that the 4-OPRI has a very low penetrance and that, perhaps, its presence is not enough to produce the disease. We would like to report a new case with four extra OPRIs (R2R2R2R3) that, in contrast to those cases described by Kaski et al. (2011), was heterozygous valine/methionine (V/M) at codon 129. The patient was a 38-year-old male, who developed rapid progressive cognitive decline with memory impairment, inattention and spatial disorientation. The EEG registers presented slow baseline rhythm but failed to show periodic sharp wave complexes. …