RT Journal Article
T1 VUS next in rare diseases? Deciphering genetic determinants of biomolecular condensation
A1 Heredia-Torrejón, María
A1 Montañez, Raúl
A1 González-Menese, Antonio
A1 Carcavilla, Atilano
A1 Lechuga-Sancho, Alfonso María
A1 Medina, Miguel Ángel
K1 Enfermedades raras
AB The diagnostic odysseys for rare disease patients are getting shorter as next-generation sequencing becomes more widespread. However, the complex genetic diversity and factors influencing expressivity continue to challenge accurate diagnosis, leaving more than 50% of genetic variants categorized as variants of uncertain significance.Genomic expression intricately hinges on localized interactions among its products. Conventional variant prioritization, biased towards known disease genes and the structure-function paradigm, overlooks the potential impact of variants shaping the composition, location, size, and properties of biomolecular condensates, genuine membraneless organelles swiftly sensing and responding to environmental changes, and modulating expressivity.To address this complexity, we propose to focus on the nexus of genetic variants within biomolecular condensates determinants. Scrutinizing variant effects in these membraneless organelles could refine prioritization, enhance diagnostics, and unveil the molecular underpinnings of rare diseases. Integrating comprehensive genome sequencing, transcriptomics, and computational models can unravel variant pathogenicity and disease mechanisms, enabling precision medicine. This paper presents the rationale driving our proposal and describes a protocol to implement this approach. By fusing state-of-the-art knowledge and methodologies into the clinical practice, we aim to redefine rare diseases diagnosis, leveraging the power of scientific advancement for more informed medical decisions.
PB BioMed Central
YR 2024
FD 2024-09-06
LK https://hdl.handle.net/10630/35309
UL https://hdl.handle.net/10630/35309
LA eng
NO Heredia-Torrejón, M., Montañez, R., González-Meneses, A. et al. VUS next in rare diseases? Deciphering genetic determinants of biomolecular condensation. Orphanet J Rare Dis 19, 327 (2024). https://doi.org/10.1186/s13023-024-03307-6
NO Funding for open access publishing: Universidad de Cádiz/CBUA. This research was funded by the Andalusian Ministry of Health and Families through the initiative (RPS 24664), code PI-0069-2022; from group BIO267 and CTS927 (Andalusian Government), and by grants PID2022-138181OB-I00 (MICINN and FEDER). The “CIBER de Enfermedades Raras” is an initiative from the ISCIII (Spain). Funding for open access publishing: Universidad de Cádiz/CBUA
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 21 ene 2026