Abstract: Objective To investigate the clinical manifestation,pathogenic genes,heredity rule,and epidemiological characteristics of rare fatal familial insomnia(FFI) in Henan province and to explore the way of prevention and control of the disease.Methods The familial migrating history and the familial disease history of FFI were collected by tracking survey among 175 familial members of 7 generations.Blood samples from the sufferers as well as some familial members were collected.Prion protein gene(PRNP) were detected with PCR and restriction fragment length polymorphism(RFLP) analysis with NspI and sequencing.The brain tissue was obtained for neuropathological test and PrP^Sc test were conducted with western blot method.Results Two diagnosed FFI cases showed typical clinical symptoms.There were 13 of 23 members of the FFI family died of similar neural disease and 20 of 90 familial members with codon mutation at D178N of PRNP and 129 allele with met/met.The gene mutation rate was 22.22% with a male/female ratio of 1:1.The age of FFI onset in the family tended gradually to be younger(anticipation) since the second generation.Conclusion The sufferers of the FFI genealogy showed typical clinical symptoms and the clustering of the disease in family was obvious.It is the largest and rare FFI family in China.