{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T08:23:08Z","timestamp":1768724588508,"version":"3.49.0"},"reference-count":150,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T00:00:00Z","timestamp":1722902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008062","name":"Alicia Koplowitz Foundation","doi-asserted-by":"publisher","award":["FAK21\/001"],"award-info":[{"award-number":["FAK21\/001"]}],"id":[{"id":"10.13039\/100008062","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of Salamanca (USAL)","award":["FAK21\/001"],"award-info":[{"award-number":["FAK21\/001"]}]},{"name":"Banco Santander","award":["FAK21\/001"],"award-info":[{"award-number":["FAK21\/001"]}]},{"name":"European Union\u2014NextGenerationEU","award":["FAK21\/001"],"award-info":[{"award-number":["FAK21\/001"]}]},{"name":"SEPE","award":["FAK21\/001"],"award-info":[{"award-number":["FAK21\/001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>RASopathies are a group of related genetic disorders caused by mutations in genes within the RAS\/MAPK signaling pathway. This pathway is crucial for cell division, growth, and differentiation, and its disruption can lead to a variety of developmental and health issues. RASopathies present diverse clinical features and pose significant diagnostic and therapeutic challenges. Studying the landscape of biomarkers in RASopathies has the potential to improve both clinical practices and the understanding of these disorders. This review provides an overview of recent discoveries in RASopathy molecular profiling, which extend beyond traditional gene mutation analysis. mRNAs, non-coding RNAs, protein expression patterns, and post-translational modifications characteristic of RASopathy patients within pivotal signaling pathways such as the RAS\/MAPK, PI3K\/AKT\/mTOR, and Rho\/ROCK\/LIMK2\/cofilin pathways are summarized. Additionally, the field of metabolomics holds potential for uncovering metabolic signatures associated with specific RASopathies, which are crucial for developing precision medicine. Beyond molecular markers, we also examine the role of histological characteristics and non-invasive physiological assessments in identifying potential biomarkers, as they provide evidence of the disease\u2019s effects on various systems. Here, we synthesize key findings and illuminate promising avenues for future research in RASopathy biomarker discovery, underscoring rigorous validation and clinical translation.<\/jats:p>","DOI":"10.3390\/ijms25168563","type":"journal-article","created":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T08:07:59Z","timestamp":1722931679000},"page":"8563","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Biomarker Landscape in RASopathies"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5167-2849","authenticated-orcid":false,"given":"Noemi","family":"Ferrito","sequence":"first","affiliation":[{"name":"Laboratory of Functional Genetics of Rare Diseases, Department of Microbiology and Genetics, University of Salamanca (USAL), 37007 Salamanca, Spain"},{"name":"GIR of Biomedicine of Rare Diseases, University of Salamanca (USAL), 37007 Salamanca, Spain"},{"name":"Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9379-4257","authenticated-orcid":false,"given":"Juan","family":"B\u00e1ez-Flores","sequence":"additional","affiliation":[{"name":"Laboratory of Functional Genetics of Rare Diseases, Department of Microbiology and Genetics, University of Salamanca (USAL), 37007 Salamanca, Spain"},{"name":"GIR of Biomedicine of Rare Diseases, University of Salamanca (USAL), 37007 Salamanca, Spain"},{"name":"Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3519-0516","authenticated-orcid":false,"given":"Mario","family":"Rodr\u00edguez-Mart\u00edn","sequence":"additional","affiliation":[{"name":"Laboratory of Functional Genetics of Rare Diseases, Department of Microbiology and Genetics, University of Salamanca (USAL), 37007 Salamanca, Spain"},{"name":"GIR of Biomedicine of Rare Diseases, University of Salamanca (USAL), 37007 Salamanca, Spain"},{"name":"Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juli\u00e1n","family":"Sastre-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Laboratory of Functional Genetics of Rare Diseases, Department of Microbiology and Genetics, University of Salamanca (USAL), 37007 Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9914-4197","authenticated-orcid":false,"given":"Alessio","family":"Coppola","sequence":"additional","affiliation":[{"name":"Laboratory of Functional Genetics of Rare Diseases, Department of Microbiology and Genetics, University of Salamanca (USAL), 37007 Salamanca, Spain"},{"name":"GIR of Biomedicine of Rare Diseases, University of Salamanca (USAL), 37007 Salamanca, Spain"},{"name":"Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda","family":"Isidoro-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain"},{"name":"Clinical Biochemistry Department, University Hospital of Salamanca, 37007 Salamanca, Spain"},{"name":"Clinical Rare Diseases Reference Unit DiERCyL, 37007 Castilla y Le\u00f3n, Spain"},{"name":"Department of Medicine, University of Salamanca (USAL), 37007 Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2680-3285","authenticated-orcid":false,"given":"Pablo","family":"Prieto-Matos","sequence":"additional","affiliation":[{"name":"GIR of Biomedicine of Rare Diseases, University of Salamanca (USAL), 37007 Salamanca, Spain"},{"name":"Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain"},{"name":"Department of Pediatrics, University Hospital of Salamanca, 37007 Salamanca, Spain"},{"name":"Department of Biomedical and Diagnostics Science, University of Salamanca (USAL), 37007 Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2751-7291","authenticated-orcid":false,"given":"Jesus","family":"Lacal","sequence":"additional","affiliation":[{"name":"Laboratory of Functional Genetics of Rare Diseases, Department of Microbiology and Genetics, University of Salamanca (USAL), 37007 Salamanca, Spain"},{"name":"GIR of Biomedicine of Rare Diseases, University of Salamanca (USAL), 37007 Salamanca, Spain"},{"name":"Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1146\/annurev-genom-091212-153523","article-title":"The RASopathies","volume":"14","author":"Rauen","year":"2013","journal-title":"Annu. 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