SPRED2 loss-of-function causes a recessive Noonan syndrome-like phenotype.

Alleles Animals COS Cells Chlorocebus aethiops HEK293 Cells Humans Loss of Function Mutation MAP Kinase Signaling System Mice Mice, Knockout Noonan Syndrome / genetics Phenotype Repressor Proteins / genetics Zebrafish
Legius syndrome MAPK Noonan syndrome RAS RASopathies SPRED SPRED1 SPRED2 neurofibromatosis neurofibromin

Journal

American journal of human genetics
ISSN: 1537-6605
Titre abrégé: Am J Hum Genet
Pays: United States
ID NLM: 0370475

Informations de publication

Date de publication:
04 11 2021
Historique:
received: 21 07 2021
accepted: 14 09 2021
pubmed: 10 10 2021
medline: 23 11 2021
entrez: 9 10 2021
Statut: ppublish

Résumé

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

Identifiants

DOI: 10.1016/j.ajhg.2021.09.007 PMID: 34626534 PMC: PMC8595899
pubmed: 34626534
pii: S0002-9297(21)00343-8
doi: 10.1016/j.ajhg.2021.09.007
pmc: PMC8595899
pii:
doi:

Substances chimiques

Repressor Proteins 0
SPRED2 protein, human 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2112-2129

Subventions

Organisme : NHLBI NIH HHS
ID : R35 HL135742
Pays : United States

Informations de copyright

Copyright © 2021 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing interests.

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Auteurs

Marialetizia Motta (M)

Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, IRCCS, 00146 Rome, Italy.

Giulia Fasano (G)

Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, IRCCS, 00146 Rome, Italy.

Sina Gredy (S)

Institute of Physiology, University of Wuerzburg, 97070 Wuerzburg, Germany.

Julia Brinkmann (J)

Institute of Human Genetics, University Hospital Magdeburg, 39120 Magdeburg, Germany.

Adeline Alice Bonnard (AA)

Assistance 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-Kiper (PO)

Department of Pediatric Genetics, Hacettepe University Faculty of Medicine, Sihhiye, 06100 Ankara, Turkey.

Elif Yilmaz Gulec (EY)

Department of Medical Genetics, Health Sciences University, Istanbul Kanuni Sultan Suleyman Training and Research Hospital, 34303 Istanbul, Turkey.

Leila Essaddam (L)

Department of Pediatrics-PUC, Béchir Hamza Children's Hospital, Faculty of Medicine, University of Tunis El Manar, Jebbari 1007, Tunis, Tunisia.

Gulen Eda Utine (GE)

Department of Pediatric Genetics, Hacettepe University Faculty of Medicine, Sihhiye, 06100 Ankara, Turkey.

Ingrid Guarnetti Prandi (I)

Dipartimento per la Innovazione nei Sistemi Biologici, Agroalimentari e Forestali, Università Della Tuscia, 01100 Viterbo, Italy.

Martina Venditti (M)

Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, IRCCS, 00146 Rome, Italy.

Francesca Pantaleoni (F)

Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, IRCCS, 00146 Rome, Italy.

Francesca Clementina Radio (FC)

Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, IRCCS, 00146 Rome, Italy.

Andrea Ciolfi (A)

Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, IRCCS, 00146 Rome, Italy.

Stefania Petrini (S)

Confocal Microscopy Core Facility, Ospedale Pediatrico Bambino Gesù, 00146 Rome, Italy.

Federica Consoli (F)

Medical Genetics Division, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy.

Cédric Vignal (C)

Assistance Publique des Hôpitaux de Paris (AP-HP), Hôpital Robert Debré, Département de Génétique, 75019 Paris, France.

Denis Hepbasli (D)

Institute of Physiology, University of Wuerzburg, 97070 Wuerzburg, Germany.

Melanie Ullrich (M)

Institute of Physiology, University of Wuerzburg, 97070 Wuerzburg, Germany.

Elke de Boer (E)

Department 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 Vissers (LELM)

Department of Human Genetics, Radboudumc, 6525 GA Nijmegen, the Netherlands; Donders Institute for Brain, Cognition and Behaviour, Radboud University, 6525 GA Nijmegen, the Netherlands.

Sami Gritli (S)

Department of Immunology, Pasteur Institute of Tunis, 1002 Tunis-Belvédère, Tunisia.

Cesare Rossi (C)

Genetica Medica, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy.

Alessandro De Luca (A)

Medical Genetics Division, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy.

Saayda Ben Becher (S)

Department of Pediatrics-PUC, Béchir Hamza Children's Hospital, Faculty of Medicine, University of Tunis El Manar, Jebbari 1007, Tunis, Tunisia.

Bruce D Gelb (BD)

Mindich Child Health and Development Institute and Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

Bruno Dallapiccola (B)

Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, IRCCS, 00146 Rome, Italy.

Antonella Lauri (A)

Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, IRCCS, 00146 Rome, Italy.

Giovanni Chillemi (G)

Dipartimento 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 Schuh (K)

Institute of Physiology, University of Wuerzburg, 97070 Wuerzburg, Germany.

Hélène Cavé (H)

Assistance 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 Zenker (M)

Institute of Human Genetics, University Hospital Magdeburg, 39120 Magdeburg, Germany.

Marco Tartaglia (M)

Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, IRCCS, 00146 Rome, Italy. Electronic address: marco.tartaglia@opbg.net.

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Classifications MeSH

questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Composants de génome › Gènes › Allèles › SPRED2 loss-of-function causes a recessive...
questionsmedicales.fr › Eucaryotes › Animaux › SPRED2 loss-of-function causes a recessive...
questionsmedicales.fr › Cellules › Cellules du tissu conjonctif › Fibroblastes › Cellules COS › SPRED2 loss-of-function causes a recessive...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Cercopithecidae › Cercopithecinae › Cercopithecus › Cercopithecus aethiops › SPRED2 loss-of-function causes a recessive...
questionsmedicales.fr › Cellules › Cellules épithéliales › Cellules HEK293 › SPRED2 loss-of-function causes a recessive...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › SPRED2 loss-of-function causes a recessive...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › Mutation perte de fonction › SPRED2 loss-of-function causes a recessive...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Système de signalisation des MAP kinases › SPRED2 loss-of-function causes a recessive...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › SPRED2 loss-of-function causes a recessive...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souris transgéniques › Souris knockout › SPRED2 loss-of-function causes a recessive...
questionsmedicales.fr › Maladies de la peau et du tissu conjonctif › Maladies du tissu conjonctif › Syndrome de Noonan › SPRED2 loss-of-function causes a recessive...
questionsmedicales.fr › Phénomènes génétiques › Phénotype › SPRED2 loss-of-function causes a recessive...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Protéines de répression › SPRED2 loss-of-function causes a recessive...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Poissons › Cypriniformes › Cyprinidae › Danio zébré › SPRED2 loss-of-function causes a recessive...