^Department of Neuropathology, Tokyo Metropolitan Institute of Geron- tology, 35-2 Sakae-cho, Itabashi-ku, Tokyo 173-0015 Japan ^Department of Neurology, Graduate School of Medicine, the University of Tokyo

Familial Creutzfeldt-Jakob disease with five octapeptide repeat insert

Yuko Saito^ Shigeo Murayama^*, Jun Shimizu^, Masataka Hoshino^, Ma- sami Takatsu^, Yasuko Komatzusaki"^, Seigo Nakano^, Kunimasa Arima^, Kensuke Sasaki^, Kei Takahashi^, Masamichi Hara^, Yoshio Hirayasu^^, Masahito Yamada^^ and Ichiro Kanazawa^

^Department of Neuropathology, Tokyo Metropolitan Institute of Geron- tology, 35-2 Sakae-cho, Itabashi-ku, Tokyo 173-0015 Japan ^Department of Neurology, Graduate School of Medicine, the University of Tokyo

^Department of Neurology, Tokyo Teishin Hospital "^Department of Neu- rology, Hatsuishi Hospital ^Department of Psychiatry & Neurology, Musashi Hospital, National Center for Neurology and Psychiatry

^Department of Neuropathology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University ^Department of Pathology, Oha- shi Hospital, Toho University ^Department of Pathology & ^^Psychiatry, Yokohama City University ^ ^Department of Neurology, Graduate School of Medicine, Kanazawa University *<e-mail> smurayam@tmig.or.jp

Abstract

A pedigree of familial CJD with five octapeptide repeat insert (50RI) is reported. In this family seven out of nine members from one generation had dementia. Three showed slowly progressive course, two with typical clinical features of CJD, and two without details. The probaband is a 62 year old man, who initially presented with abnormal behavior at age 52.

The symptoms gradually deteriorated into a bed-ridden state with no ver- bal expression at age 59. There was no 14-3-3- protein in CSF or PSD in EEG. MRI showed cerebral atrophy with T2 high intensity of the white matter. At age 62, he still responds to a call for his name. The pro- band's oldest brother showed similar clinical features, starting difficulty in word recall around age 64, followed by progressive mental deterioration but was ambulatory even just prior to death. He died unexpectedly and no autopsy was done. The other two brothers showed typical clinical features of CJD, with onset at age 41 and 51, respectively. Their clinical course was about one year, accompanying myoclonus, PSD and akinetic mutism. The brain weight was l,320g and l,260g respectively. In the

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cerebral cortex, severe neuronal loss and gliosis with spongiformic

changes were present. Hippocampus was relatively spared. The cere-

bellum showed severe depletion of granular cells. Immunocytochemi-

cally the deposition of prion protein was of synaptic pattern in the cerebral

cortex and confluent granular one in the cerebellar cortex. In addition,

degeneration of the cerebral white matter was diffuse in one case but focal

in another. In the latter case, 50RI was detected. So far, the results of

the sequence analysis differ in two other reported families with 50RI. A

current family may provide a direct evidence that two distinct phenotypes

of rapidly or slowly progressive clinical course may arise from the same

50RI sequence abnormality.