河南省一例致死性家族性失眠症病例研究

Analysis for clinical and genetic characteristics of a sporadic FFI case

目的调查和研究报道1例散发型致死性家族性失眠症（sporadic Family Fatalisomnia，sFFI）的临床症状，分析人类朊病毒病（Human prion protein，PrP）基因特征。方法随访调查1例疑为FFI患者的临床特征和家族发病史；采集患者脑脊液及抗凝全血标本后Western．Blot检测14-3-3脑蛋白及常染色体PrP基因突变及测序分析；采集患者家族成员抗凝全血进行PrP基因突变检测。结果根据患者的临床表现及PrP基因检测结果，PrP呈D178N／129M／M突变基因型；且脑蛋白14—3．3阳性，这在以往少有报道，提示今后在临床鉴别、诊断人类克-雅病（CJD）与FFI患者时，应注重甄别临床症状及实验室结果；14名直系及旁系家族成员PrP基因均未出现突变，且家族内无其他人患类似疾病。结论该患者为致死性家族性失眠症单发性病例；患者的临床表现及PrP基因突变检测对甄别单发、家族聚集性的致死性失眠症及人类CJD作用重大。该FFI病例为我国首次报道，具有较大的临床意义和科研意义。

Objective To report and study a case of sporadic family fatal insomnia（SFFI）on its.Methods Investigate clinical characteristics and family disease history of a suspect FFI patient His clinical characteristic was analyzed, he and his 14 family members genomic DNA was extracted by standard techniques from their and blood detected with polymerase chain reaction（PCR）method and DNA sequencing to find out his prion protein （PrP）gene mutation. The patient＇s CSF was detected with Western-Blot method for 14-3-3 brain protein. Results The patient was diagnosed as an sporadic FFI by his developed sleep disturbance and ehanges in sleep-awake rhythm, motor abnormalities, mental disorder, dementia, autonomic dysfunction ; his family history ; his 14-3-3 brain protein, positive （CSF） and analysis results of his PrP gene （eodon point mutation D178N and methionine homozygosity at position 129M/M）. Suggesting that in the future to identify CJD and FFI patients, screening should focus on clinical symptoms and laboratory results. The PrP gene of 14 family members did not appear Mutation, and there is no person suffering from the same disease. Conclusions The case was diagnosed as a sporadic familial fatal insomnia. Analysis of suspicious patients＇genomic DNA for PrP gene mutation might be very important for FFI diagnosis because there exist many difficulties in clinical laboratory evaluation. This patient might be the first SFFI patient reported in China and the case finding might have momentousness in clinical and basical study.