TY  - JOUR
AU  - Da Silva Correia, Angela
AU  - Laginha, Ines
AU  - Guimaraes, Susana
AU  - Dittmar, Kathrin
AU  - Schmitz, Matthias
AU  - Castilla, Joaquin
AU  - Zerr, Inga
AU  - Silva-Correia, Susana
TI  - Pedigree analysis and genetic inheritance of fatal familial insomnia (FFI) in a Portuguese multigenerational family.
JO  - Journal of neurology
VL  - 272
IS  - 10
SN  - 0367-004X
CY  - [Darmstadt]
PB  - Steinkopff
M1  - DZNE-2025-01183
SP  - 706
PY  - 2025
AB  - Fatal familial insomnia (FFI) is a rare, autosomal dominant prion disease caused by a mutation in the PRNP gene, leading to the misfolding of the cellular prion protein (PrPC) into its pathogenic form (PrPSc). This results in neurodegeneration, particularly in the thalamus, a key region regulating sleep-wake cycles, which underlies the hallmark symptoms of FFI, including insomnia, autonomic dysfunctions, motor disturbances and cognitive decline. This study focuses on a Portuguese family with FFI, providing a detailed pedigree analysis spanning five generations and comprising 134 individuals, to elucidate inheritance patterns, disease onset, and clinical progression. The findings confirm the autosomal-dominant inheritance pattern and a strong familial clustering of the disease with age of onset in the late 50s (mean 57 years). Although 67
KW  - Humans
KW  - Insomnia, Fatal Familial: genetics
KW  - Insomnia, Fatal Familial: physiopathology
KW  - Male
KW  - Middle Aged
KW  - Portugal
KW  - Female
KW  - Pedigree
KW  - Adult
KW  - Prion Proteins: genetics
KW  - Aged
KW  - Age of Onset
KW  - Disease Progression
KW  - Extended Family
KW  - FFI (Other)
KW  - Fatal familial insomnia (Other)
KW  - Portugal (Other)
KW  - PrPC (Other)
KW  - PrPSc (Other)
KW  - Prion diseases (Other)
KW  - Prion Proteins (NLM Chemicals)
KW  - PRNP protein, human (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:41107634
C2  - pmc:PMC12534306
DO  - DOI:10.1007/s00415-025-13432-2
UR  - https://pub.dzne.de/record/281793
ER  -