Rare V180I mutation in PRNP gene of a Chinese patient with Creutzfeldt-Jakob disease

Abstract

Abstract Here, we reported a Chinese case of Creutzfeldt-Jakob disease (CJD) with a rare mutation in the prion protein gene (PRNP) leading to an exchange of amino acid from valine (V) to isoleucine (I) at codon 180 (V180I). The 72 year-old Chinese women started with gradual memory loss. On admission, she did not present special abnormality during clinical examinations except bradykinesia in her lower extremities. Myoclonic jerks and increased muscle tone were noticed 3 months after the onset. No periodic activity was recorded at electroencephalography (EEG) and 14-3-3 protein was negative in the cerebrospinal fluid (CSF) sample. Brain diffusion weighted images (DWI) demonstrated high signal intensities in bilateral frontal, parietal, temporal and occipital cortices, especially on the left hemisphere, and high signal intensities were also seen in the left caudate nucleus and the putamen. The patient had no family history of similar symptoms. Her general condition was gradually deteriorative, but the patient was still alive when we performed the follow-up 12 months after onset.

Keywords: 14-3-3 protein; Creutzfeldt–Jakob disease; PRNP; V180I; mutation.

Figure 1.

Diffusion weighted brain MRIs show high signal intensity in diffuse cerebral cortex with dominant involvement of left hemisphere (arrows). High signal intensities were also seen in the left caudate nucleus and the putamen (arrowheads).

Figure 2.

Western blot analysis of 14-3-3 protein in CSF samples. Positive ctrl: 10% goat brain homogenate. Negative ctrl: a human CSF sample previously confirmed to be 14-3-3 negative. Case sample: the CSF sample of the present V180I gCJD case. M: commercial prestained protein molecular markers whose relative molecular weights are shown on the left.

Figure 3.

Graphic presentation of the sequencing analysis of PRNP. The left graph shows the DNA sequence of the patient at codon 180 shows a G to A heterozygous transition at codon 180 in one PRNP allele, leading to an exchange from Val (V) to Ile (I). The right graph shows a control of the DNA sequence of a person containing Val/Val homozygote at codon 180 in PRNP alleles.

Figure 4.

Graphic presentations of homozygosity for methionine at codon 129 (left) and homozygosity for glutamate at codon 219 (right) in the sequencing analysis of PRNP gene of the present V180I gCJD patient.