Clinical and Laboratory Features of Three Rare Chinese V210I gCJD Patients

Abstract

Genetic human prion diseases are a group of inherited encephalopathies directly associated with different mutations in PrP-encoding gene PRNP, including more than 50 different mutations worldwide. Some genotypes of mutations show ethno-correlation, and among them, genetic Creutzfeldt-Jacob disease (gCJD) with V210I mutation is frequent in European countries but rare in East Asia. Here, we comparatively analyzed the clinical and laboratory features of three Chinese patients with V210I mutant identified via the Chinese National CJD Surveillance System (CNS-CJD) in 2019. Two cases were Han Chinese and one was Hui Chinese, without blood kinship. The onset ages of three cases were 69, 64, and 59 years old, respectively. The clinical features of V210I gCJD were similar to sporadic CJD (sCJD), displaying typical clinical symptoms and signs, except that Case 3 did not show myoclonic movement. All three cases displayed sCJD-associated abnormalities on MRI and positive CSF 14-3-3, while two cases recorded typical EEG abnormalities. Only one case was positive in CSF real-time quaking-induced conversion (RT-QuIC). Appearances of mutism in three cases were relatively fast, with the intervals of 30 to 50 days after onset. Family history was not reported in all three cases. Those V210I gCJD cases are rare in China, and probably the first three in East Asia.

Keywords: PRNP; V210I; genetic Creutzfeldt–Jacob disease; prion.

Figure 1

Western blot for 14-3-3. 15 μL of CSF sample each patient was subjected into 12% SDS-PAGE. Blots were incubated in 1:1,000 diluted 14-3-3 polyclonal antibodies (Santa Cruz, CA, USA) and further incubated in 1:5,000 diluted HRP-conjugated goat anti-Rabbit IgG (PerkinElmer, Germany). Immunoreactive bands were visualized by ECL method (PerkinElmer, Germany). M: molecular standards. (+): positive control of 10% goat brain homogenate. Arrows indicate the CSF samples of the individual V210I gCJD patients.

Figure 2

Results of RT-QuIC assays of CSF samples of three V210I gCJD Chinese patients. 10⁻⁵ diluted brain homogenate of scrapie agent 263K infected hamster was used as positive control and that of normal hamster was used as negative control. ThT value is showed in Y-axis and hour post-reaction is indicated in X-axis.

Figure 3

Graphic presentations of the sequences of PRNP from 3 Chinese V210I gCJD patients by direct sequencing. G/A heterozygote at codon 210 are detected, leading to an exchange from Val (V) to Ile (I). The arrows below the curves indicate the positions where both G and A are co-present.