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Activating Mutation...
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Cordeddu, VivianaIst Super Sanita, Italy; University of G dAnnunzio, Italy
(author)
Activating Mutations Affecting the Dbl Homology Domain of SOS2 Cause Noonan Syndrome
- Article/chapterEnglish2015
Publisher, publication year, extent ...
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2015-08-03
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WILEY-BLACKWELL,2015
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printrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:liu-122516
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https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-122516URI
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https://doi.org/10.1002/humu.22834DOI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Funding Agencies|National Institutes of Health [R01 HL071207, R01 HL0832732, U01 DE020060, R01 HG003988, U54 HG006997, U54 HG006504]; Telethon-Italy [GGP13107]; AIRC [IG 13360]; Ministry of Health [RF-2011-02349938]; Princess Margaret Cancer Foundation; Ontario Ministry of Health and Long Term Care; CIHR CGS-D
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The RASopathies constitute a family of autosomal-dominant disorders whose major features include facial dysmorphism, cardiac defects, reduced postnatal growth, variable cognitive deficits, ectodermal and skeletal anomalies, and susceptibility to certain malignancies. Noonan syndrome (NS), the commonest RASopathy, is genetically heterogeneous and caused by functional dysregulation of signal transducers and regulatory proteins with roles in the RAS/extracellular signal-regulated kinase (ERK) signal transduction pathway. Mutations in known disease genes account for approximately 80% of affected individuals. Here, we report that missense mutations altering Son of Sevenless, Drosophila, homolog 2 (SOS2), which encodes a RAS guanine nucleotide exchange factor, occur in a small percentage of subjects with NS. Four missense mutations were identified in five unrelated sporadic cases and families transmitting NS. Disease-causing mutations affected three conserved residues located in the Dbl homology (DH) domain, of which two are directly involved in the intramolecular binding network maintaining SOS2 in its autoinhibited conformation. All mutations were found to promote enhanced signaling from RAS to ERK. Similar to NS-causing SOS1 mutations, the phenotype associated with SOS2 defects is characterized by normal development and growth, as well as marked ectodermal involvement. Unlike SOS1 mutations, however, those in SOS2 are restricted to the DH domain.
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Added entries (persons, corporate bodies, meetings, titles ...)
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Yin, Jiani C.University of Toronto, Canada; University of Toronto, Canada
(author)
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Gunnarsson, CeciliaLinköpings universitet,Avdelningen för cellbiologi,Medicinska fakulteten,Region Östergötland, Klinisk patologi och klinisk genetik(Swepub:liu)cecgu53
(author)
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Virtanen, CarlUniversity of Toronto, Canada; University of Toronto, Canada
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Drunat, SeverineHop Robert Debre, France
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Lepri, FrancescaBambino Gesu Pediat Hospital, Italy
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De Luca, AlessandroCasa Sollievo Sofferenza Hospital, Italy
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Rossi, CesareSt Orsola Marcello Malpighi Hospital, Italy
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Ciolfi, AndreaIst Super Sanita, Italy
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Pugh, Trevor J.University of Toronto, Canada; University of Toronto, Canada
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Bruselles, AlessandroIst Super Sanita, Italy
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Priest, James R.Stanford University, CA 94305 USA; Stanford University, CA 94305 USA
(author)
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Pennacchio, Len A.University of Calif Berkeley, CA 94720 USA; US Department Energy Joint Genome Institute, CA 94598 USA
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Lu, ZhibinUniversity of Toronto, Canada; University of Toronto, Canada
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Danesh, ArnavazUniversity of Toronto, Canada; University of Toronto, Canada
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Quevedo, ReneUniversity of Toronto, Canada; University of Toronto, Canada
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Hamid, AlaaUniversity of Toronto, Canada; University of Toronto, Canada
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Martinelli, SimoneIst Super Sanita, Italy
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Pantaleoni, FrancescaIst Super Sanita, Italy
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Gnazzo, MariaBambino Gesu Pediat Hospital, Italy
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Daniele, PaolaCasa Sollievo Sofferenza Hospital, Italy
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Lissewski, ChristinaOtto von Guericke University, Germany
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Bocchinfuso, GianfrancoUniversity of Roma Tor Vergata, Italy
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Stella, LorenzoUniversity of Roma Tor Vergata, Italy
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Odent, SylvieHop SUD, France
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Philip, NicoleHop Enfants la Timone, France
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Faivre, LaurenceHop Enfants, France
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Vlckova, MarketaCharles University of Prague, Czech Republic; University Hospital Motol, Czech Republic
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Seemanova, EvaCharles University of Prague, Czech Republic; University Hospital Motol, Czech Republic
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Digilio, CristinaBambino Gesu Pediat Hospital, Italy
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Zenker, MartinOtto von Guericke University, Germany
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Zampino, GiuseppeUniversity of Cattolica Sacro Cuore, Italy
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Verloes, AlainHop Robert Debre, France
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Dallapiccola, BrunoBambino Gesu Pediat Hospital, Italy
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Roberts, Amy E.Boston Childrens Hospital, MA 02115 USA; Boston Childrens Hospital, MA 02115 USA
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Cave, HeleneHop Robert Debre, France; University of Paris Diderot, France
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Gelb, Bruce D.Icahn School Medical Mt Sinai, NY 10029 USA; Icahn School Medical Mt Sinai, NY 10029 USA; Icahn School Medical Mt Sinai, NY 10029 USA
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Neel, Benjamin G.University of Toronto, Canada; University of Toronto, Canada; NYU, NY 10016 USA
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Tartaglia, MarcoIst Super Sanita, Italy; Bambino Gesu Pediat Hospital, Italy
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Ist Super Sanita, Italy; University of G dAnnunzio, ItalyUniversity of Toronto, Canada; University of Toronto, Canada
(creator_code:org_t)
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In:Human Mutation: WILEY-BLACKWELL36:11, s. 1080-10871059-77941098-1004
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Cordeddu, Vivian ...
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Yin, Jiani C.
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Gunnarsson, Ceci ...
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Virtanen, Carl
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Drunat, Severine
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Lepri, Francesca
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De Luca, Alessan ...
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Rossi, Cesare
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Ciolfi, Andrea
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Pugh, Trevor J.
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Bruselles, Aless ...
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Priest, James R.
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Pennacchio, Len ...
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Lu, Zhibin
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Danesh, Arnavaz
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Quevedo, Rene
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Hamid, Alaa
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Martinelli, Simo ...
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Pantaleoni, Fran ...
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Gnazzo, Maria
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Daniele, Paola
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Lissewski, Chris ...
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Bocchinfuso, Gia ...
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Stella, Lorenzo
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Odent, Sylvie
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Philip, Nicole
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Faivre, Laurence
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Vlckova, Marketa
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Seemanova, Eva
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Digilio, Cristin ...
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Zenker, Martin
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Zampino, Giusepp ...
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Verloes, Alain
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Dallapiccola, Br ...
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Roberts, Amy E.
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Cave, Helene
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Gelb, Bruce D.
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Neel, Benjamin G ...
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Tartaglia, Marco
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Human Mutation
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Linköping University