A Chinese genetic prion disease:clinical,pathological manifestation and prion protein gene mutation analysis / 中华神经科杂志

ABSTRACT

Objective To report a large family with an autosomal dominant dementia associated with mutation in the prion protein gene(PRNP)and the detailed clinical,neuroimaging and pathological manifestations.Methods Two patients from a large family of dementia were admitted to our ward and the data of their medical history,physical examination,video electroenceplialogram,neuroimaging were colleted.A sterotactic biopsy of the right frontal lobe of the proband was done.After the informed consent from the family members obtained,the genomic DNA was extracted from peripheral blood leucocytes of 5 persons followed by in,vitro amplification using polymerase chain reaction(PCR).The PCR products were directly sequenced by Sanger method.PRNP gene sequence was also examined in 150 normal Chinese to exclude single nueleotide polymorphism.Results A missense mutation of PRNP gene in 5 farnily members was detected,resulting in Gll4V mutation in the prion protein,with M/M genotype of eodon 129.This mutation was not detected in 150 normal Chinese.The proband was diagnosed as inherited prion disease by her clinical features,including neuropsychiatrie disturbances and progressive dementia,and manifestations of neuroimaging,EEG,neuropathology and PRNP gene mutation.Conclusion The first autosomal dominant pedigree of family prion disease is found in China with G114V mutation in PRNP gene which may lead to the prion disease directly.