title: Evidence for a pathogenic role of different mutations at codon 188 of PRNP.
abstract: Clinical and pathological changes in familial Creutzfeldt-Jakob disease (CJD) cases may be similar or indistinguishable from sporadic CJD. Therefore determination of novel mutations in PRNP remains of major importance. We identified two different rare mutations in codon 188 of the prion protein gene (PRNP) in four patients suffering from a disease clinically very similar to the major subtype of sporadic CJD. Both mutations result in an exchange of the amino acid residue threonine for a highly basic residue, either arginine (T188R) or lysine (T188K). The T188R mutation was found in one patient and the T188K mutation in three patients. The prevalence of mutations at codon 188 of PRNP was tested in 593 sporadic CJD cases and 735 healthy individuals. Neither mutation was found. The data presented here argue in favor of T188K being a pathogenic mutation causing genetic CJD. Since one individual with this mutation, who is the father of a clinically affected patient with T188K mutation, is now 79 years old and shows no signs of disease, this mutation is likely associated with a penetrance under 100%. Further observations will have to show whether T188R is a pathogenic mutation.
authors.affiliation: Center for Neuropathology and Prion Research, Ludwig-Maximilians-University, München, Germany.
authors.forename: Sigrun
authors.initials: S
authors.lastname: Roeber
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Grasbon-Frodl
authors.forename: Otto
authors.initials: O
authors.lastname: Windl
authors.forename: Bjarne
authors.initials: B
authors.lastname: Krebs
authors.forename: Wei
authors.initials: W
authors.lastname: Xiang
authors.forename: Caren
authors.initials: C
authors.lastname: Vollmert
authors.forename: Thomas
authors.initials: T
authors.lastname: Illig
authors.forename: Andreas
authors.initials: A
authors.lastname: Schröter
authors.forename: Thomas
authors.initials: T
authors.lastname: Arzberger
authors.forename: Petra
authors.initials: P
authors.lastname: Weber
authors.forename: Inga
authors.initials: I
authors.lastname: Zerr
authors.forename: Hans A
authors.initials: HA
authors.lastname: Kretzschmar
mesh_terms: D000368:Aged; D001483:Base Sequence; D001706:Biopsy; D015153:Blotting, Western; D001921:Brain / Q000473:pathology; D003062:Codon; D007562:Creutzfeldt-Jakob Syndrome / Q000235:genetics* / Q000473:pathology; D017931:DNA Primers; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D000072002:Prion Proteins; D011328:Prions / Q000235:genetics*
chemical_list: D003062:Codon; D017931:DNA Primers; C512656:PRNP protein, human; D000072002:Prion Proteins; D011328:Prions