Pedigree analysis and genetic inheritance of fatal familial insomnia (FFI) in a Portuguese multigenerational family.

ABSTRACT: 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 o

SUBMITTER: Da Silva Correia A 

PROVIDER: S-EPMC12534306 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature