Materials and MethodsĤ0 diagnosed D178N/M129M FFI cases via China CJD surveillance program were enrolled into this study. The RT-QuIC reactive profiles of the CSF samples from 39 patients and those of the brain samples from 3 patients were also proposed. In this study, the epidemiological, clinical, genetic and laboratory characteristics of these 40 FFI cases were comparatively investigated based on the disease family history, gender and the onsetage. Up to June 2017, 40 FFI cases were diagnosed by the center of CJD surveillance system under the framework of China CDC, making up about 33% of all diagnosed genetic prion diseases. Based on the surveillance data for human prion disease in China, FFI is most frequently detected genetic prion disease. FFI may occur without family history, or with definite clinical family history and/or genetic evidence. Afterwards, FFI cases have been reported in many countries and regions, as well as in different races. įFI was firstly described in an Italian family in 1986. Pathologically, instead of spongiform degeneration and PrPSc deposits that are frequently observable in the brains of sporadic CJD (sCJD), which is the predominant type of human prion disease, and majority of human genetic prion disease, FFI is characterized by severe neuron loss and active astrogliosis in some brain regions, especially thalamus. However, clinically FFI displays completely different phenotype, characterized by a disordered sleep-wake cycle, dysautonomia and motor signs. Same as other human genetic prion diseases, including genetic or familial Creutzfeldt-Jakob disease (gCJD or fCJD) and Gerstmann-Sträussler- Scheinker diseases (GSS), FFI is an autosomal dominant heredopathy. Genetically, FFI is linked to a GAC to AAC point mutation (substitution from aspartic acid to asparagines) at codon 178 of the prion protein gene ( PRNP) (D178N). Keywordsįatal familial insomnia, Genetic prion disease, PRNP sequencing, D178N mutation Introductionįatal familial insomnia (FFI) is a special subtype of human genetic prion disease which prominent pathology is occurs mainly in the thalamus, showing severe astrogliosis and loss of neurons. This is the largest study on FFI patients in China, as well as in Asia, which is helpful to enrich the knowledge of FFI. The median survival was 10 months varying from 5 to 30 months. 126 individual from 14 families conducted prion gene (PRNP) sequencing and 36 asymptomatic carriers of D178N mutation and M129M homozygous were identified, among them 7 mutation carriers from 5 families were in the parent-generation and 5 from 3 families were elder siblings of the probands. Sporadic Creutzfeldt-Jakob disease (sCJD) associated abnormalities on MRI were recorded only in 6 patients with the onset-age ≥ 50 y. 37.9% cases were cerebrospinal fluid (CSF) 14-3-3 positive and 25% were CSF RT-QuIC positive. 85% patients showed hypertension and 57.5% had obvious weight loss. Sympathetic symptoms, such as excessive sweating, salivation and minor evening pyrexia, were commonly noticed. Sleeping disturbances, mental problems and recognition disorders were most common foremost symptoms, in which sleeping disturbances and recognition disorders were significantly frequent in the patients with positive family history and those with the onset age ≥ 50 y, respectively. 45% cases displayed clinical symptoms less than 50 y and 32.5% cases did not have definitely disease family history. The median onset age was 51 year-old (from 19-70 y) and the gender ratio was 1:1.5 (M:F). Despite of the distribution in 12 provinces, apparently more cases located in Henan and Guangdong provinces. In this study, the epidemiological, clinical, laboratory and genetic features of 40 Chinese FFI patients were systematically analyzed.
National Institute for Viral Disease Control and Prevention, Chinese Center for Disease, Control and Prevention, Chang-Bai Rd 155, Beijing 102206, Chinaįatal familial insomnia (FFI) is one of the subtypes of human genetic prion diseases and is the most frequently identified genetic prion disease in China. State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, China *Corresponding Author: Xiao-Ping Dong Qi Shi, Kang Xiao, Wei Zhou, Jing Wang, Cao Chen, Chen Gao and Xiao-Ping Dong *
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