Characteristics of Chinese patients with genetic CJD who have E196A or E196K mutation in PRNP: comparative analysis of patients identified in the Chinese National CJD Surveillance System

OBJECTIVE: Two different mutations at codon 196, namely E196A and E196K, have been reported to be related to genetic Creutzfeldt-Jakob disease (CJD). We aimed to comparatively analyse the features of Chinese patients with these two mutations from the CJD surveillance system in China. DESIGN AND SETTING: Comparative analysis of patients identified via the Chinese National CJD Surveillance System during the period 2006–2020. PARTICIPANTS: 16 Chinese patients with genetic CJD with E196A mutation and 5 with E196K mutation. METHODS: Neurological examination, EEG and MRI, western blot, gene sequence, and RT-QuIC. RESULTS: The age of onset of E196K genetic CJD cases (median of 61 years) was older than the E196A cases (median of 67 years). Generally, these two subtypes of genetic CJD were more like sporadic Creutzfeldt-Jakob disease (sCJD) clinically. The E196A cases showed more major symptoms, while those of E196K cases were restricted to dementia and mental problems. During progression, more sCJD-associated symptoms and signs gradually appeared, but none of the E196K cases showed cerebellum and visual disturbances. Typical periodic sharp wave complexes on MRI were recorded in 25% of E196A cases but not in E196K cases. sCJD-associated abnormalities on MRI, positive cerebrospinal fluid (CSF) 14-3-3 and increased CSF total tau were observed frequently, ranging from two out of three cases to four out of five cases, without a difference. Positive CSF RT-QuIC was detected in 37.5% (6 of 16) of E196A cases and 60% (3 of 5) of E196K cases. The duration of survival of E196K cases (median of 4.5 months) was shorter than the E196A cases (median of 6.5 months). Moreover, female cases and cases with young age of onset (<60 years) in E196A displayed longer survival time than male patients and cases with older age of onset (≥60 years). CONCLUSIONS: This is the largest comprehensive report of genetic CJD with mutations at codon 196 to date, describing the similarity and diversity in clinical and laboratory tests between patients with E196A and with E196K mutations.