The Risk of Transmission of Genetic Prion Diseases is Greater Than 50%
This study provides the first systematic evidence of TRD in inherited prion diseases, with both variants showing clinically meaningful deviations from Mendelian inheritance. These findings challenge current genetic counseling assumptions of 50% inheritance risk and suggest that actual transmission probabilities are 17%-21% higher than traditionally estimated. Risk assessment protocols for prion diseases require updating to incorporate variant-specific and sex-specific transmission patterns, particularly the strong paternal bias observed with p.E200K.
Authors
- Guiomar Pérez de Nanclares (ORCID: https://orcid.org/0000-0002-2424-5294)
- Izaro Kortazar‐Zubizarreta (ORCID: https://orcid.org/0000-0002-8107-660X)
- Hasier Eraña (ORCID: https://orcid.org/0000-0001-8776-4211)
- Joaquı́n Castilla (ORCID: https://orcid.org/0000-0002-2216-1361)
- Urko Aguire
- África Manero-Azua (ORCID: https://orcid.org/0000-0001-8176-0463)
Institutions
- Ikerbasque (ES)
- Instituto de Salud Carlos III (ES)
- Euskadiko Parke Teknologikoa (ES)
- Red de Investigación en Actividades Preventivas y Promoción de la Salud (ES)
- Hospital Txagorritxu (ES)
- Hospital Universitario Araba (ES)
- CIC bioGUNE (ES)
- Centro de Investigación Biomédica en Red (ES)
- Osasun Sistemen Ikerketa Institutua (ES)
- Hospital de Galdakao (ES)
Publication Details
- Journal
- European Journal of Neurology
- Published
- 2025-12-01
- DOI
- https://doi.org/10.1111/ene.70455
- Primary Topic
- Prion Diseases and Protein Misfolding
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- EU Joint Programme – Neurodegenerative Disease Research
- European Commission
- Ministerio de Ciencia e Innovación
- Instituto de Salud Carlos III
- European Regional Development Fund
- Agencia Estatal de Investigación
- Interreg