RT journal article
T1 VUS next in rare diseases? Deciphering genetic determinants of biomolecular condensation
A1 Heredia Torrejon, María
A1 Montañez, R.
A1 González-Meneses, A.
A1 Carcavilla, A.
A1 Medina, M.A.
A1 Lechuga Sancho, Alfonso María
A2 Materno-Infantil y Radiología
K1 Biomolecular condensation
K1 Genetic variant prioritization
K1 Intrinsically disordered protein regions
K1 LLPS
K1 Molecular diagnosis
K1 Molecular effects of genetic variations
K1 Rare diseases
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 Ltd
SN 1750-1172
YR 2024
FD 2024
LK http://hdl.handle.net/10498/35636
UL http://hdl.handle.net/10498/35636
LA eng
DS Repositorio Institucional de la Universidad de Cádiz
RD 22-sep-2026