{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:32:45Z","timestamp":1790775165509,"version":"4.1.0"},"reference-count":169,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,10,1]],"date-time":"2022-10-01T00:00:00Z","timestamp":1664582400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Noonan syndrome (NS) and related Noonan syndrome with multiple lentigines (NSML) contribute to the pathogenesis of human diseases in the RASopathy family. This family of genetic disorders constitute one of the largest groups of developmental disorders with variable penetrance and severity, associated with distinctive congenital disabilities, including facial features, cardiopathies, growth and skeletal abnormalities, developmental delay\/mental retardation, and tumor predisposition. NS was first clinically described decades ago, and several genes have since been identified, providing a molecular foundation to understand their physiopathology and identify targets for therapeutic strategies. These genes encode proteins that participate in, or regulate, RAS\/MAPK signalling. The RAS pathway regulates cellular metabolism by controlling mitochondrial homeostasis, dynamics, and energy production; however, little is known about the role of mitochondrial metabolism in NS and NSML. This manuscript comprehensively reviews the most frequently mutated genes responsible for NS and NSML, covering their role in the current knowledge of cellular signalling pathways, and focuses on the pathophysiological outcomes on mitochondria and energy metabolism.<\/jats:p>","DOI":"10.3390\/cells11193099","type":"journal-article","created":{"date-parts":[[2022,10,8]],"date-time":"2022-10-08T01:52:21Z","timestamp":1665193941000},"page":"3099","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Effects of Noonan Syndrome-Germline Mutations on Mitochondria and Energy Metabolism"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5066-1398","authenticated-orcid":false,"given":"Donald","family":"Bajia","sequence":"first","affiliation":[{"name":"Department of Pediatric Oncology, Hematology and Transplantology, Poznan University of Medical Sciences, Ul. Fredry 10, 61701 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1217-8722","authenticated-orcid":false,"given":"Emanuela","family":"Bottani","sequence":"additional","affiliation":[{"name":"Department of Diagnostics and Public Health, Section of Pharmacology, University of Verona, Piazzale L. A. Scuro 10, 37134 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna","family":"Derwich","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Hematology and Transplantology, Poznan University of Medical Sciences, Ul. Fredry 10, 61701 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1016\/j.bbabio.2018.05.003","article-title":"RAS signalling in energy metabolism and rare human diseases","volume":"1859","author":"Dard","year":"2018","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1210\/er.2017-00232","article-title":"The RASopathy Family: Consequences of Germline Activation of the RAS\/MAPK Pathway","volume":"39","author":"Tajan","year":"2018","journal-title":"Endocr. Rev."},{"key":"ref_3","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. Rev. Genom. Hum. 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