Editing Fatal insomnia (section)

==Cause==
{{Technical|section|date=September 2023}}
[[Image:Location of PRNP-gene in chromosome 20.svg|thumb|250px|[[Idiogram]] of chromosome 20 showing gene'' PRP ''location]]
Fatal familial insomnia is a rare hereditary [[prion]] disease that is associated with a mutation in ''PRNP''. The gene, which provides instructions for making the [[prion protein]] PrP<sup>C</sup>, is located on the short arm of [[chromosome 20]] at position p13.<ref>{{cite web|url=http://ghr.nlm.nih.gov/gene/PRNP |title=PRNP gene |website=Genetics Home Reference |access-date=22 March 2018}}</ref> Individuals with FFI or familial [[Creutzfeldt–Jakob disease]] (fCJD) both carry a mutation at [[codon]] 178 of the prion protein gene. FFI is also invariably linked to the presence of the [[methionine]] codon at position 129 of the mutant allele, whereas fCJD is linked to the presence of the [[valine]] codon at that position. The disease occurs when there is a change of [[amino acid]] at position 178 in which [[asparagine]] is found instead of the normal [[aspartic acid]]. This has to be accompanied with a methionine at position 129.<ref>{{cite book | vauthors = Khan Z, Sankari A, Bollu PC |title=StatPearls |date=2024 |publisher=StatPearls Publishing |chapter=Fatal Familial Insomnia |chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK482208/ |pmid=29489284 }}</ref>

FFI is an autosomal dominant disease caused by a [[Missense mutation|missense GAC-to-AAC mutation]] at codon 178 of the ''PRNP'' prion protein gene located on chromosome 20, along with the presence of the methionine polymorphism at position 129 of the mutant allele. Pathologically, FFI is characterized predominantly by [[Thalamus|thalamic]] degeneration{{em dash}}especially in the [[Medial dorsal nucleus|medio-dorsal]] and [[Anteroventral periventricular nucleus|anteroventral nuclei]].<ref>{{cite journal | vauthors = Xie K, Chen Y, Chu M, Cui Y, Chen Z, Zhang J, Liu L, Jing D, Cui C, Liang Z, Ren L, Rosa-Neto P, Ghorayeb I, Zhang Z, Wu L | title = Specific structuro-metabolic pattern of thalamic subnuclei in fatal familial insomnia: A PET/MRI imaging study | journal = NeuroImage. Clinical | volume = 34 | pages = 103026 | date = 2022 | pmid = 35504222 | pmc = 9065920 | doi = 10.1016/j.nicl.2022.103026 }}</ref> [[Phenotypic heterogeneity|Phenotypic variability]] is a perplexing feature of FFI.<ref>{{cite journal | vauthors = Zhang J, Chu M, Tian Z, Xie K, Cui Y, Liu L, Meng J, Yan H, Ji YM, Jiang Z, Xia TX, Wang D, Wang X, Zhao Y, Ye H, Li J, Wang L, Wu L | title = Clinical profile of fatal familial insomnia: phenotypic variation in 129 polymorphisms and geographical regions | journal = Journal of Neurology, Neurosurgery, and Psychiatry | volume = 93 | issue = 3 | pages = 291–297 | date = March 2022 | pmid = 34667102 | pmc = 8862016 | doi = 10.1136/jnnp-2021-327247 }}</ref>

Prion diseases are caused by the accumulation of misfolded prion proteins in the brain. Generally, prion disorders are characterized by long incubation periods and short clinical duration, which means the abnormal prions may accumulate for many years without causing symptoms (long incubation period), but once symptoms begin the disorder rapidly worsens.