Objective Fatal familial insomnia （FFI） is an autosomal dominant prion disease characterized clinically by inattention, sleep loss, dysautonomia, and motor signs. This study is aimed to investigate clinical and fami...Objective Fatal familial insomnia （FFI） is an autosomal dominant prion disease characterized clinically by inattention, sleep loss, dysautonomia, and motor signs. This study is aimed to investigate clinical and familial characteristics often Chinese Patients with FFI. Methods We identified ten FFI cases from the surveillance network for Creutafeldt- Jakob disease （CJD） in China.Final diagnosis of FFI cases was made in accordance with the WHO criteria for CJD.The main clinical features and family histories of these ten FFI cases were analyzed. Results The median age of ten cases at onset was 38 years （from 19 to 55）. The foremost symptoms seemed to be various, including sleep disturbances, vision disorder, dizziness and anorexia. Sleep disturbances appeared in all cases and lasted in the whole clinical courses. Progressive sympathetic symptoms, memory loss, movement disturbances, myoclonus and hypertension were also frequently observed. The median duration of the disease was 9.5 months. EEG and MRI did not figure out special abnormality. 14-3-3 protein in CSF was positive in five out of eight tested patients. Clear family histories were identified in 8 patients. Conclusion The data from our study confirm that the Chinese FFI cases have similar clinical characteristics as that of the Caucasian cases. Compared with other genetic CJD associated mutations, the genetic frequencies of D178N in PRNP are apparently high among the Chinese cases.展开更多
Human genetic prion diseases(gPrDs)are directly associated with mutations and insertions in the PRNP(Prion Protein)gene.We collected and analyzed the data of 218 Chinese gPrD patients identified between Jan 2006 and J...Human genetic prion diseases(gPrDs)are directly associated with mutations and insertions in the PRNP(Prion Protein)gene.We collected and analyzed the data of 218 Chinese gPrD patients identified between Jan 2006 and June 2020.Nineteen different subtypes were identified and gPrDs accounted for 10.9%of all diagnosed PrDs within the same period.Some subtypes of gPrDs showed a degree of geographic association.The age at onset of Chinese gPrDs peaked in the 50–59 year group.Gerstmann–Sträussler–Scheinker syndrome(GSS)and fatal familial insomnia(FFI)cases usually displayed clinical symptoms earlier than genetic Creutzfeldt–Jakob disease(gCJD)patients with point mutations.A family history was more frequently recalled in P105L GSS and D178N FFI patients than T188K and E200K patients.None of the E196A gCJD patients reported a family history.The gCJD cases with point mutations always developed clinical manifestations typical of sporadic CJD(sCJD).EEG examination was not sensitive for gPrDs.sCJD-associated abnormalities on MRI were found in high proportions of GSS and gCJD patients.CSF 14-3-3 positivity was frequently detected in gCJD patients.Increased CSF tau was found in more than half of FFI and T188K gCJD cases,and an even higher proportion of E196A and E200K gCJD patients.63.6%of P105L GSS cases showed a positive reaction in cerebrospinal fluid RT-QuIC.GSS and FFI cases had longer durations than most subtypes of gCJD.This is one of the largest studies of gPrDs in East Asians,and the illness profile of Chinese gPrDs is clearly distinct.Extremely high proportions of T188K and E196A occur among Chinese gPrDs;these mutations are rarely reported in Caucasians and Japanese.展开更多
基金supported by China Mega-Project for Infectious Disease(2009ZX10004-101,2008ZX)SKLID Development Grant(2008SKLID102,2011SKLID211)+3 种基金National Basic Research Program of China(973 Program)(2007CB310505)sponsored by the Young Scholar Scientific Research Foundation of China CDC(2012A102)Chinese National Natural Science Foundation Grants 30771914 and 30800975 Institution Technique R&D Grant(2008EG150300)
文摘Objective Fatal familial insomnia （FFI） is an autosomal dominant prion disease characterized clinically by inattention, sleep loss, dysautonomia, and motor signs. This study is aimed to investigate clinical and familial characteristics often Chinese Patients with FFI. Methods We identified ten FFI cases from the surveillance network for Creutafeldt- Jakob disease （CJD） in China.Final diagnosis of FFI cases was made in accordance with the WHO criteria for CJD.The main clinical features and family histories of these ten FFI cases were analyzed. Results The median age of ten cases at onset was 38 years （from 19 to 55）. The foremost symptoms seemed to be various, including sleep disturbances, vision disorder, dizziness and anorexia. Sleep disturbances appeared in all cases and lasted in the whole clinical courses. Progressive sympathetic symptoms, memory loss, movement disturbances, myoclonus and hypertension were also frequently observed. The median duration of the disease was 9.5 months. EEG and MRI did not figure out special abnormality. 14-3-3 protein in CSF was positive in five out of eight tested patients. Clear family histories were identified in 8 patients. Conclusion The data from our study confirm that the Chinese FFI cases have similar clinical characteristics as that of the Caucasian cases. Compared with other genetic CJD associated mutations, the genetic frequencies of D178N in PRNP are apparently high among the Chinese cases.
基金This work was supported by the National Natural Science Foundation of China(81630062)the State Key Laboratory for Infectious Disease Prevention and Control,CDC,China(2019SKLID501,2019SKLID603,and 2019SKLID307).
文摘Human genetic prion diseases(gPrDs)are directly associated with mutations and insertions in the PRNP(Prion Protein)gene.We collected and analyzed the data of 218 Chinese gPrD patients identified between Jan 2006 and June 2020.Nineteen different subtypes were identified and gPrDs accounted for 10.9%of all diagnosed PrDs within the same period.Some subtypes of gPrDs showed a degree of geographic association.The age at onset of Chinese gPrDs peaked in the 50–59 year group.Gerstmann–Sträussler–Scheinker syndrome(GSS)and fatal familial insomnia(FFI)cases usually displayed clinical symptoms earlier than genetic Creutzfeldt–Jakob disease(gCJD)patients with point mutations.A family history was more frequently recalled in P105L GSS and D178N FFI patients than T188K and E200K patients.None of the E196A gCJD patients reported a family history.The gCJD cases with point mutations always developed clinical manifestations typical of sporadic CJD(sCJD).EEG examination was not sensitive for gPrDs.sCJD-associated abnormalities on MRI were found in high proportions of GSS and gCJD patients.CSF 14-3-3 positivity was frequently detected in gCJD patients.Increased CSF tau was found in more than half of FFI and T188K gCJD cases,and an even higher proportion of E196A and E200K gCJD patients.63.6%of P105L GSS cases showed a positive reaction in cerebrospinal fluid RT-QuIC.GSS and FFI cases had longer durations than most subtypes of gCJD.This is one of the largest studies of gPrDs in East Asians,and the illness profile of Chinese gPrDs is clearly distinct.Extremely high proportions of T188K and E196A occur among Chinese gPrDs;these mutations are rarely reported in Caucasians and Japanese.
