Clinical, histopathological and genetic studies in a family with fatal familial insomnia.
We compared clinical data from two related Chinese patients with fatal familial insomnia (FFI) and collected information about their pedigree. The clinical features in the two cases were similar and included initial progressive insomnia and sympathetic activation, which persisted throughout the clinical course. A total of 135 members of this family, across seven generations, were retrospectively investigated. Eleven family members, including the two FFI cases, were found to have died with similar neurological problems. Analysis of PRNP in 32 family members revealed eleven carrying the D178N allele, including the two FFI patients. Spongiform degeneration in brains was not found, but gliosis was obvious in the thalamus of the two cases at postmortem. Proteinase K-resistant prion protein (PrP) was not found in proband's brain by immunohistochemistry, but observed in some areas of brain for both cases by PrP-specific Western blot. Investigation of the pedigree has led to the identification of an additional 9 family members who had similar clinical symptoms and 9 currently healthy individuals with the D178N mutation.
Shi
Xiao-Hong
XH
Department of Neurology, Henan Province People's Hospital, Zhengzhou, China.
Han
Jun
J
Zhang
Jin
J
Shi
Qi
Q
Chen
Jian-Ming
JM
Xia
Sheng-Li
SL
Xie
Zhi-Qiang
ZQ
Shen
Xiao-Jing
XJ
Shan
Bing
B
Lei
Yan-Jun
YJ
Shi
Song
S
Zhou
Wei
W
Zhang
Bao-Yun
BY
Gao
Chen
C
Liu
Ying-Hui
YH
Song
Juan
J
Guo
Yan-Jun
YJ
Wang
De-Xin
DX
Xu
Bian-Li
BL
Dong
Xiao-Ping
XP
D000328:Adult; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D019286:Endopeptidase K / Q000378:metabolism; D005260:Female; D006651:Histocytochemistry; D006801:Humans; D034062:Insomnia, Fatal Familial / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D000072002:Prion Proteins; D011328:Prions / Q000235:genetics
C512656:PRNP protein, human; D000072002:Prion Proteins; D011328:Prions; D019286:Endopeptidase K