A case of Creutzfeldt-Jakob disease with a novel insertion mutation and codon 219 Lysine/Lysine polymorphism in the prion protein gene
Y. Nishida\ N. Sodeyama\ Y.
TOYU\ S.Toru\ T. Kitamoto^ and H. Mi- zusawa^
^The Department of Neurology and Neurological Science, Graduate School, Tokyo Medical and Dental University, Tokyo, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519 Japan ^Department of Neurological Sci- ence, Tohoku University, School of Medicine
<e-mail> y-nishida.nuro@tmd.ac.jp
Abstract
Introduction
A prion disease patient with codon 219 Lysine (Lys) homozygote has not been reported. We present a patient with Creutzfeldt-Jakob disease (CJD) carrying two outstanding genetic features in the prion protein gene (PRNP): a novel mutation of three-time octapeptide insertion and a codon 219 Lys/Lys polymorphism.
Patient report
A 68-year-old Japanese man developed gait disturbance and vertigo.
Three months after the onset, cognitive functions were severely impaired with diffuse hyperreflexia, rigidity, akinesia and parkinsonian gait. The levels of 14-3-3 and tau proteins in cerebrospinal fluid (CSF) were normal.
EEG showed periodic synchronous discharges with generalized slowing.
MRI on diffusion weighted sequences revealed widespread hyperintensi- ties in the cerebral cortices and striatum. He became apallic 13 months after the onset. He died of pneumonia three years after the onset. There was no myoclonus throughout his clinical course. In PRNP, there was a 72-basepair insertion between codons 51 and 91, consisting of a single re- peat of 24 nucleotides (R3g) and double repeats of another normal 24 nu- cleotides (R2). The R3g had an A-to-G transition at the last position of
251
252