Evidence for a pathogenic role of different mutations at codon 188 of PRNP

Roeber, Sigrun; Grasbon-Frodl, Eva-Maria; Windl, Otto; Krebs, Bjarne; Xiang, Wei; Vollmert, Caren; Illig, Thomas; Schröter, Andreas; Arzberger, Thomas; Weber, Petra; Zerr, Inga und Kretzschmar, Hans A. (14. Mai 2008): Evidence for a pathogenic role of different mutations at codon 188 of PRNP.
In: PLOS ONE 3(5), e2147

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.

• Dokumententyp: Zeitschriftenartikel
• Publikationsform: Publisher's Version
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1932-6203
• Bemerkung: This study was supported by a grant from the Federal Ministry of Health (Bundesgesundheitsministerium) and the European Commission (TSELAB QLK 2- CT-2002-81523). Genotyping in this study was partially supported within the German National Genomic Research Network (01GS0166) by the Federal Ministry of Education and Research (BMBF). The KORA research platform (KORA, Cooperative Research in the Region of Augsburg) was initiated and financed by the GSF-National Research Centre for Environment and Health, which is funded by the German Federal Ministry of Education and Research and of the State of Bavaria. Erratum in PLoS ONE. 2008;3(5). doi: 10.1371/annotation/3189bbdc-e736-4cb5-b1f2-9a5fb49536c6.
• Sprache: Englisch