河南省致死性家族性失眠症家系的流行病学调查及遗传规律研究

摘要

目的 调查致死性家族性失眠症(FFI)家系谱特征及家族发病史;分析病例的临床特点和病理学改变;研究FFI家系的流行病学特征及相关基因遗传规律.方法 通过7代135名家族成员的流行病学调查,了解家族史、家族迁徙史及发病史;对患者及部分家族成员抽取静脉血进行PRNP基因PCR扩增,序列测定和Nsp I酶切鉴定;尸检采集脑组织进行神经病理学检测和Western blot法PrPCc蛋白检测.结果 2例确诊患者临床症状典型;11名家族成员死于相似的神经性疾病;32名家族成员血标本检测,其中11人出现PRNP基因178位密码子点突变(D178N),突变检出率34.38%,第129位密码子为甲硫氨酸;病例脑组织海绵样变性和神经元缺失,可检测到PrPSc蛋白.结论 该家系为FFI家系,病例临床症状典型,病理特征明显.流行病学调查、基因特征分析、神经病理学和Westernblot法检测对确立FFI病例和家系有至关重要的作用.%Objective To investigate the epidemiological,genealogic characteristic,familial history of the families with fatal familial insomnia,its clinical and pathological features as well as the heredity rule of related genes.Methods 135 familial members of 7 eras were studied.Vein blood samples from patients as well as from some familial members were collected.PRNP gene was studied with PCR,its serial was determined and then authenticated with Nsp I.Brain tissue was obtained for neuropathological test and PrPSc test with Western blot method.Results Clinical symptoms of the 2 diagnosed cases were typical.11 familial members died of similar neural disease.32 samples of their familial members,codon at D178N of PRNP of 11 members was mutated,with mutation rate as 34.38% while D129N showed as methionine.Brain tissue of both probands denaturalized into spongiform and the nerve fiber was absent but PrPSc protein was identified.Conclusion Genealogy was described in the family with fatal familial insomnia since the patients had typical clinical symptoms and pathological characteristics.It seemed necessary to confirm cases of fatal familial insomnia and their genealogy with epidemiological data and to investigate its gene characteristics as well as with neuropathological and Western blot tests.