Creutzfeldt–Jakob disease associated with a T188K homozygous mutation in the prion protein gene: a case report and review of the literature

Figures & data

Figure 1. Pedigree of this case. gCJD, genetic Creutzfeldt–Jakob disease; AO, age of onset (year); DD, duration from onset to death (year). Circles indicate females; squares indicate males; yellow symbols indicate affected individuals; diagonal bars indicate deceased members; black arrow indicates the pro-band.

Figure 2. Timeline of the clinical manifestations and the results of examinations of this case. MRI, magnetic resonance imaging; DWI, diffusion-weighted imaging; FDG-PET, ¹⁸Fluorodeoxyglucose-positron emission tomography; EEG, electroencephalography.

Figure 3. (a) Axial serial diffusion-weighted MRI showing restricted diffusion involving the right striatum, cerebellar cortex and cortical ribboning of the temporal and insular cortices; (b) ¹⁸Fluorodeoxyglucose-positron emission tomography showing severe glucose hypometabolism in the bilateral cerebellar cortex and mild glucose hypometabolism in the right frontoparietal cortex; (c) PRNP sequencing showing a homozygous substitution: c.563 C > A (p.T188K).

Table 1. Clinical and investigational features of patients with homozygous mutations in the PRNP.

Author, year, country	Age at onset (years), sex	Homozygote mutation	Codon 129	Initial clinical manifestation	Hyperintensity on DWI	PSWCs in EEG	CSF 14–3–3 protein	Disease duration, (months)
Komatsu et al, 2014, Japan	72, F	V203I	M/M	Cognitive dysfunction, gait disturbance	Basal ganglia, cerebral cortex	+	+	24
Nitsan et al, 2020, Israel	40, M	E200K	NA	Behavioural changes, 40%; cognitive decline, 30%; focal neurologic deficits, 20%; cerebellar symptoms, 0%	NA	NA	NA	4
	51, M	E200K	NA		NA	NA	NA	10
	56, M	E200K	NA		NA	NA	NA	74
	49, M	E200K	NA		NA	NA	NA	17
	41, F	E200K	NA		NA	NA	NA	15
	51, M	E200K	NA		NA	NA	NA	97
	53, M	E200K	NA		NA	NA	NA	4
	42, M	E200K	NA		NA	NA	NA	4
	40, F	E200K	NA		NA	NA	NA	2
	49, M	E200K	NA		NA	NA	NA	30
Hassan et al, 2021, UK	61, M	E200D	M/M	Cognitive dysfunction, gait disturbance	Basal ganglia, cerebral cortex	-	-	3
Present patient, Chinese	47, F	T188K	M/M	Diplopia, dizziness, gait disturbance	Basal ganglia, cerebral cortex, cerebellar cortex	-	-	15

PRNP, prion protein gene; DWI, diffusion-weighted imaging; PSWCs, periodic sharp wave complexes; EEG, electroencephalography; CSF, cerebrospinal fluid; NA, not available.