Familial Creutzfeldt-Jakob disease with a point mutation (Met to Arg) at codon 232: two different phenotypes

Familial Creutzfeldt-Jakob disease with a point mutation (Met to Arg) at codon 232: two different phenotypes

Yusei Shiga^ Hideki Mizuno^ Shohei Watanabe^ Maki Tateyama^ Ichiro Nakashima\ Kazuo Fujihara^ Tetsuyuki Kitamoto^ and Yasuto Itoyama^

^Department of Neurology and ^Division of CJD Science and Technology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aoba-ku, Sendai 980-8575 Japan

<e-mail> yshiga@em.neurol.med.tohoku.ac.jp

Abstract

Objectives

10 to 15% of Creutzfeldt-Jakob disease (CJD) cases are estimated to be familial. CJD with a causative point mutation of methionine to arginine at codon 232 (M232R) is a type of familial CJD (CJD232). We report here two cases of CJD232 with different clinical features.

Case report

Patient 1

A 5 5-year-old woman who had no family history of dementia developed insomnia followed by somnolence, intellectual deterioration, unsteady gait, psychiatric symptoms and myoclonus. Two months after the onset, she was admitted to our hospital because of severe dementia. EEG showed periodic sharp and wave complexes (PSWC) and diffusion-weighted MRI (DWI) demonstrated a high intensity lesion in the bilateral striatum.

14-3-3 protein immunoassay in CSF was positive. Prion protein gene (PRNP) analysis revealed M232R and methionine homozygosity at codon

129 (MM 129). Three months after the onset she became akinetic and mute.

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Case 2

A 70-year-old woman who had no family history of dementia developed memory disturbance followed by paranoia and insomnia. Four months after the onset she was admitted to our hospital because of progressing dementia. EEG showed no PSWC and DWI demonstrated a high inten- sity lesion in the wide range of bilateral cerebral cortex, thalamus, and striatum. 14-3-3 protein immunoassay was positive. PRNP analysis revealed M232R and MM 129. Nine monthes after the onset, she was in a state of severe dementia but did not become akinetic and mute. EEG showed no PSWC.

Discussion

Many cases of familial CJD caused by PRNP abnormalities have been re- ported and some of the clinical features are different from those of spo- radic CJD. However, the clinical features of familial CJD are regulated by the genotype of PRNP. The clinical features of our patients were quite different from each other; one showed rapidly progressing dementia, gen- eralized myoclonus, and PSWC in EEG, whereas the other showed rela- tively slowly progressing dementia, no myoclonus, and no PSWC.

However, the genotype of PRNP was the same including the polymor-

phism of codon 129. To date, nine rapid patients and six slowly patients

with the same genotype have been recognized. There are two phenotypes

in familial CJD with M232R and some factors apart from the genotype in-

fluence the phenotype.