ArticleAmerican journal of human genetics2021
SPRED2 loss-of-function causes a recessive Noonan syndrome-like phenotype.
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Article in American journal of human genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 3 of them syntheses that pooled it.
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40citing papers in PubMed, 3 pooled it
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40 citing papers in PubMed, 3 syntheses or guidelines pooled it, 79 citations in OpenAlex.
- Genome-wide analysis of heart failure yields insights into disease heterogeneity and enables prognostic prediction in the Japanese population.Nature communications · 2025Pooled it
- Update on the Clinical and Molecular Characterization of Noonan Syndrome and Other RASopathies: A Retrospective Study and Systematic Review.International journal of molecular sciences · 2025Pooled it
- Abnormalities of pubertal development and gonadal function in Noonan syndrome.Frontiers in endocrinology · 2023Pooled it
- Clinical and Molecular Characterization of a RASopathy Cohort From Türkiye and an AMMECR1-Related Noonan Syndrome-Mimicking Phenotype.Clinical genetics · 2026Article
- Clinical consensus guidelines for the management of Noonan syndrome in Japan.Clinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology · 2026Article
- Clinical and Genetic Characterization of Noonan Syndrome in a Colombian Pediatric CohortJournal of clinical research in pediatric endocrinology · 2026Observational
- TRIM25 Suppresses Hippocampal Neuronal Autophagy under High Glucose via Ubiquitination and Degradation of SIX2.Journal of molecular neuroscience : MN · 2026Article
- A Novel HeterozygousInternational journal of molecular sciences · 2026Article
- Deficiency of anterior pituitary hormones in Noonan syndrome and its impact on response to growth hormone therapy.World journal of clinical pediatrics · 2025Article
- The impact of RAS on cell differentiation in health and disease.The Biochemical journal · 2025Review
- Article
- BiallelicInternational journal of molecular sciences · 2025Article
- Loss of SPRED3 Causes Primary Hypothyroidism and Alters Thyroidal Expression of Autophagy Regulators LC3, p62, and ATG5 in Mice.International journal of molecular sciences · 2025Article
- Wnt/β-catenin activation by mutually exclusive FBXW11 and CTNNB1 hotspot mutations drives salivary basal cell adenoma.Nature communications · 2025Article
- Molecular Dynamics Simulations of the SPRED2International journal of molecular sciences · 2025Article
- Rescuing DNMT1 fails to fully reverse the molecular and functional repercussions of its loss in mouse embryonic stem cells.Nucleic acids research · 2025Article
- Article
- Update on Pediatric Cancer Surveillance Recommendations for Patients with Neurofibromatosis Type 1, Noonan Syndrome, CBL Syndrome, Costello Syndrome, and Related RASopathies.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Review
- Dominantly acting variants in ATP6V1C1 and ATP6V1B2 cause a multisystem phenotypic spectrum by altering lysosomal and/or autophagosome function.HGG advances · 2024Article
- SMAD4 mutations causing Myhre syndrome are under positive selection in the male germline.American journal of human genetics · 2024Article
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Authors and funding
33 authors at 14 institutions in 7 countries.
Marialetizia MottaGenetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, IRCCS, 00146 Rome, Italy.
Giulia FasanoGenetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, IRCCS, 00146 Rome, Italy.
Sina GredyInstitute of Physiology, University of Wuerzburg, 97070 Wuerzburg, Germany.
Julia BrinkmannInstitute of Human Genetics, University Hospital Magdeburg, 39120 Magdeburg, Germany.
Adeline Alice BonnardAssistance Publique des Hôpitaux de Paris (AP-HP), Hôpital Robert Debré, Département de Génétique, 75019 Paris, France; INSERM UMR 1131, Institut de Recherche Saint-Louis, Université de Paris, Paris, France.
Pelin Ozlem Simsek-KiperDepartment of Pediatric Genetics, Hacettepe University Faculty of Medicine, Sihhiye, 06100 Ankara, Turkey.
Elif Yilmaz GulecDepartment of Medical Genetics, Health Sciences University, Istanbul Kanuni Sultan Suleyman Training and Research Hospital, 34303 Istanbul, Turkey.
Leila EssaddamDepartment of Pediatrics-PUC, Béchir Hamza Children's Hospital, Faculty of Medicine, University of Tunis El Manar, Jebbari 1007, Tunis, Tunisia.
Gulen Eda UtineDepartment of Pediatric Genetics, Hacettepe University Faculty of Medicine, Sihhiye, 06100 Ankara, Turkey.
Ingrid Guarnetti PrandiDipartimento per la Innovazione nei Sistemi Biologici, Agroalimentari e Forestali, Università Della Tuscia, 01100 Viterbo, Italy.
Martina VendittiGenetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, IRCCS, 00146 Rome, Italy.
Francesca PantaleoniGenetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, IRCCS, 00146 Rome, Italy.
Francesca Clementina RadioGenetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, IRCCS, 00146 Rome, Italy.
Andrea CiolfiGenetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, IRCCS, 00146 Rome, Italy.
Stefania PetriniConfocal Microscopy Core Facility, Ospedale Pediatrico Bambino Gesù, 00146 Rome, Italy.
Federica ConsoliMedical Genetics Division, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy.
Cédric VignalAssistance Publique des Hôpitaux de Paris (AP-HP), Hôpital Robert Debré, Département de Génétique, 75019 Paris, France.
Denis HepbasliInstitute of Physiology, University of Wuerzburg, 97070 Wuerzburg, Germany.
Melanie UllrichInstitute of Physiology, University of Wuerzburg, 97070 Wuerzburg, Germany.
Elke de BoerDepartment of Human Genetics, Radboudumc, 6525 GA Nijmegen, the Netherlands; Donders Institute for Brain, Cognition and Behaviour, Radboud University, 6525 GA Nijmegen, the Netherlands.
Lisenka E L M VissersDepartment of Human Genetics, Radboudumc, 6525 GA Nijmegen, the Netherlands; Donders Institute for Brain, Cognition and Behaviour, Radboud University, 6525 GA Nijmegen, the Netherlands.
Sami GritliDepartment of Immunology, Pasteur Institute of Tunis, 1002 Tunis-Belvédère, Tunisia.
Cesare RossiGenetica Medica, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy.
Alessandro De LucaMedical Genetics Division, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy.
Saayda Ben BecherDepartment of Pediatrics-PUC, Béchir Hamza Children's Hospital, Faculty of Medicine, University of Tunis El Manar, Jebbari 1007, Tunis, Tunisia.
Bruce D GelbMindich Child Health and Development Institute and Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Bruno DallapiccolaGenetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, IRCCS, 00146 Rome, Italy.
Antonella LauriGenetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, IRCCS, 00146 Rome, Italy.
Giovanni ChillemiDipartimento per la Innovazione nei Sistemi Biologici, Agroalimentari e Forestali, Università Della Tuscia, 01100 Viterbo, Italy; Istituto di Biomembrane, Bioenergetica e Biotecnologie Molecolari, Centro Nazionale Delle Ricerche, 70126 Bari, Italy.
Kai SchuhInstitute of Physiology, University of Wuerzburg, 97070 Wuerzburg, Germany.
Hélène CavéAssistance Publique des Hôpitaux de Paris (AP-HP), Hôpital Robert Debré, Département de Génétique, 75019 Paris, France; INSERM UMR 1131, Institut de Recherche Saint-Louis, Université de Paris, Paris, France.
Martin ZenkerInstitute of Human Genetics, University Hospital Magdeburg, 39120 Magdeburg, Germany.
Marco TartagliaGenetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, IRCCS, 00146 Rome, Italy. Electronic address: marco.tartaglia@opbg.net.
Bambino Gesù Children's Hospital · ITUniversity of Würzburg · DECasa Sollievo della Sofferenza · ITChildren's Hospital · TNHacettepe University · TRRadboud University Nijmegen · NLUniversità degli Studi della Tuscia · ITUniversity Hospital Magdeburg · DEUniversity of London Institute in Paris · FRAssistance Publique – Hôpitaux de Paris · FRChild Health and Development Institute · USInstitut Pasteur de Tunis · TNMedica (Italy) · ITSağlık Bilimleri Üniversitesi · TR
Funding
Pediatric Heart Disease: Getting from Mutations to TherapeuticsR35HL135742 · NHLBI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI GELB, BRUCE D · 2017 to 2023
$6.1MNHLBI NIH HHS R35 HL135742
Abstract
Upregulated signal flow through RAS and the mitogen-associated protein kinase (MAPK) cascade is the unifying mechanistic theme of the RASopathies, a family of disorders affecting development and growth. Pathogenic variants in more than 20 genes have been causally linked to RASopathies, the majority having a dominant role in promoting enhanced signaling. Here, we report that SPRED2 loss of function is causally linked to a recessive phenotype evocative of Noonan syndrome. Homozygosity for three different variants-c.187C>T (p.Arg63
Indexed as
Loss of Function MutationPhenotypeAllelesAnimalsChlorocebus aethiopsCOS CellsHEK293 CellsHumansMAP Kinase Signaling SystemMiceMice, KnockoutNoonan SyndromeRepressor ProteinsZebrafishRepressor ProteinsSPRED2 protein, humanLegius syndromeMAPKneurofibromatosisneurofibrominNoonan syndromeRASRASopathiesSPREDSPRED1SPRED2
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