title: Does the clinical phenotype of fatal familial insomnia depend on PRNP codon 129 methionine-valine polymorphism?
abstract: Fatal familial insomnia (FFI) is a rare, hereditary prion-protein disease. Methionine-valine polymorphism at codon 129 of the prion-protein gene (PRNP) determines the phenotype in other hereditary prion-protein diseases, but association with the clinical phenotype in FFI remains uncertain. Early clinical findings in FFI comprise disturbances of the sleep-wake cycle and mild neuropsychiatric changes which typically emerge during middle to late adulthood. Here we describe an unusually early onset and rapid progression of FFI associated with dorsal midbrain involvement in a female patient with PRNP mutation at codon 178 and homozygote methionine polymorphism at codon 129. Early dorsal midbrain involvement became apparent by total loss of REM sleep and isolated bilateral trochlear nerve palsy. Early onset and rapid progression disease type associated with dorsal midbrain involvement may indicate a different spatiotemporal distribution of the neurodegenerative process in FFI patients with PRNP mutation and codon 129 methionine homozygosity compared to methioninevaline heterozygosity.
authors: Hans-Berger-Department of Neurology, Jena University Hospital, Germany ; Center for Sepsis Control and Care, Jena University Hospital, Germany.
authors: Sven
authors: S
authors: Rupprecht
authors: Alexander
authors: A
authors: Grimm
authors: Torsten
authors: T
authors: Schultze
authors: Jan
authors: J
authors: Zinke
authors: Panagiota
authors: P
authors: Karvouniari
authors: Hubertus
authors: H
authors: Axer
authors: Otto W
authors: OW
authors: Witte
authors: Matthias
authors: M
authors: Schwab
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging; D003062:Codon / Q000235:genetics*; D003937:Diagnosis, Differential; D017809:Fatal Outcome; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D034062:Insomnia, Fatal Familial / Q000175:diagnosis* / Q000235:genetics*; D008715:Methionine; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics / Q000502:physiology; D017286:Polysomnography / Q000379:methods; D049268:Positron-Emission Tomography / Q000379:methods; D000072002:Prion Proteins; D011328:Prions / Q000235:genetics*; D019275:Radiopharmaceuticals; D014057:Tomography, X-Ray Computed / Q000379:methods; D014633:Valine; D055815:Young Adult
chemical_list: D003062:Codon; C512656:PRNP protein, human; D000072002:Prion Proteins; D011328:Prions; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D008715:Methionine; D014633:Valine
keywords: Fatal familiar insomnia; methionine-valine polymorphism; sleep regulation; thalamic degeneration; trochlear palsy