AustralieFrV1, Main, Exploration, bibRecord, 000B52

Genotype and phenotype spectrum of NRAS germline variants.

Identifieur interne : 000B52 ( Main/Exploration ); précédent : 000B51; suivant : 000B53

Genotype and phenotype spectrum of NRAS germline variants.

Auteurs : Franziska Altmüller [Allemagne] ; Christina Lissewski [Allemagne] ; Debora Bertola [Brésil] ; Elisabetta Flex [Italie] ; Zornitza Stark [Australie] ; Stephanie Spranger [Allemagne] ; Gareth Baynam [Australie] ; Michelle Buscarilli [Brésil] ; Sarah Dyack [Canada] ; Jane Gillis [Canada] ; Helger G. Yntema [Pays-Bas] ; Francesca Pantaleoni [Italie] ; Rosa Le Van Loon [Pays-Bas] ; Sara Mackay [Canada] ; Kym Mina [Australie] ; Ina Schanze [Allemagne] ; Tiong Yang Tan [Australie] ; Maie Walsh [Australie] ; Susan M. White [Australie] ; Marena R. Niewisch [Allemagne] ; Sixto García-Mi Aúr [Espagne] ; Diego Plaza [Espagne] ; Mohammad Reza Ahmadian [Allemagne] ; Hélène Cavé [France] ; Marco Tartaglia [Italie] ; Martin Zenker [Allemagne]

Source :

European journal of human genetics : EJHG [ 1476-5438 ] ; 2017.

RBID : pubmed:28594414

Descripteurs français

English descriptors

KwdEn :
- Adolescent, Adult, Child, Child, Preschool, Costello Syndrome (genetics), Costello Syndrome (pathology), Ectodermal Dysplasia (genetics), Ectodermal Dysplasia (pathology), Facies, Failure to Thrive (genetics), Failure to Thrive (pathology), Female, GTP Phosphohydrolases (genetics), Genotype, Germ-Line Mutation, Heart Defects, Congenital (genetics), Heart Defects, Congenital (pathology), Humans, Infant, Infant, Newborn, Male, Membrane Proteins (genetics), Mutation, Missense, Noonan Syndrome (genetics), Noonan Syndrome (pathology), Phenotype.
MESH :
- chemical , genetics : GTP Phosphohydrolases, Membrane Proteins.
- genetics : Costello Syndrome, Ectodermal Dysplasia, Failure to Thrive, Heart Defects, Congenital, Noonan Syndrome.
- pathology : Costello Syndrome, Ectodermal Dysplasia, Failure to Thrive, Heart Defects, Congenital, Noonan Syndrome.
- Adolescent, Adult, Child, Child, Preschool, Facies, Female, Genotype, Germ-Line Mutation, Humans, Infant, Infant, Newborn, Male, Mutation, Missense, Phenotype.

Abstract

RASopathies comprise a group of disorders clinically characterized by short stature, heart defects, facial dysmorphism, and varying degrees of intellectual disability and cancer predisposition. They are caused by germline variants in genes encoding key components or modulators of the highly conserved RAS-MAPK signalling pathway that lead to dysregulation of cell signal transmission. Germline changes in the genes encoding members of the RAS subfamily of GTPases are rare and associated with variable phenotypes of the RASopathy spectrum, ranging from Costello syndrome (HRAS variants) to Noonan and Cardiofaciocutaneous syndromes (KRAS variants). A small number of RASopathy cases with disease-causing germline NRAS alterations have been reported. Affected individuals exhibited features fitting Noonan syndrome, and the observed germline variants differed from the typical oncogenic NRAS changes occurring as somatic events in tumours. Here we describe 19 new cases with RASopathy due to disease-causing variants in NRAS. Importantly, four of them harbored missense changes affecting Gly12, which was previously described to occur exclusively in cancer. The phenotype in our cohort was variable but well within the RASopathy spectrum. Further, one of the patients (c.35G>A; p.(Gly12Asp)) had a myeloproliferative disorder, and one subject (c.34G>C; p.(Gly12Arg)) exhibited an uncharacterized brain tumour. With this report, we expand the genotype and phenotype spectrum of RASopathy-associated germline NRAS variants and provide evidence that NRAS variants do not spare the cancer-associated mutation hotspots.

DOI: 10.1038/ejhg.2017.65
PubMed: 28594414

Affiliations:

Le document en format XML

<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Genotype and phenotype spectrum of NRAS germline variants.</title>
<author><name sortKey="Altmuller, Franziska" sort="Altmuller, Franziska" uniqKey="Altmuller F" first="Franziska" last="Altmüller">Franziska Altmüller</name>
<affiliation wicri:level="3"><nlm:affiliation>Institute of Human Genetics, University Hospital Magdeburg, Magdeburg, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institute of Human Genetics, University Hospital Magdeburg, Magdeburg</wicri:regionArea>
<placeName><region type="land" nuts="2">Saxe-Anhalt</region>
<settlement type="city">Magdebourg</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Lissewski, Christina" sort="Lissewski, Christina" uniqKey="Lissewski C" first="Christina" last="Lissewski">Christina Lissewski</name>
<affiliation wicri:level="3"><nlm:affiliation>Institute of Human Genetics, University Hospital Magdeburg, Magdeburg, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institute of Human Genetics, University Hospital Magdeburg, Magdeburg</wicri:regionArea>
<placeName><region type="land" nuts="2">Saxe-Anhalt</region>
<settlement type="city">Magdebourg</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Bertola, Debora" sort="Bertola, Debora" uniqKey="Bertola D" first="Debora" last="Bertola">Debora Bertola</name>
<affiliation wicri:level="4"><nlm:affiliation>Unidade de Genética do Instituto da Criança-Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.</nlm:affiliation>
<country xml:lang="fr">Brésil</country>
<wicri:regionArea>Unidade de Genética do Instituto da Criança-Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo</wicri:regionArea>
<placeName><settlement type="city">São Paulo</settlement>
<region type="state">État de São Paulo</region>
<settlement type="city">São Paulo</settlement>
</placeName>
<orgName type="university">Université de São Paulo</orgName>
</affiliation>
</author>
<author><name sortKey="Flex, Elisabetta" sort="Flex, Elisabetta" uniqKey="Flex E" first="Elisabetta" last="Flex">Elisabetta Flex</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.</nlm:affiliation>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome</wicri:regionArea>
<placeName><settlement type="city">Rome</settlement>
<region nuts="2">Latium</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Stark, Zornitza" sort="Stark, Zornitza" uniqKey="Stark Z" first="Zornitza" last="Stark">Zornitza Stark</name>
<affiliation wicri:level="3"><nlm:affiliation>Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne</wicri:regionArea>
<placeName><settlement type="city">Melbourne</settlement>
<region type="état">Victoria (État)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Spranger, Stephanie" sort="Spranger, Stephanie" uniqKey="Spranger S" first="Stephanie" last="Spranger">Stephanie Spranger</name>
<affiliation wicri:level="3"><nlm:affiliation>Praxis für Humangenetik, Bremen, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Praxis für Humangenetik, Bremen</wicri:regionArea>
<placeName><region type="land" nuts="3">Brême (Land)</region>
<settlement type="city">Brême</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Baynam, Gareth" sort="Baynam, Gareth" uniqKey="Baynam G" first="Gareth" last="Baynam">Gareth Baynam</name>
<affiliation wicri:level="1"><nlm:affiliation>Genetic Services of Western Australia, WA Department of Health, Perth, Western Australia, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Genetic Services of Western Australia, WA Department of Health, Perth, Western Australia</wicri:regionArea>
<wicri:noRegion>Western Australia</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Buscarilli, Michelle" sort="Buscarilli, Michelle" uniqKey="Buscarilli M" first="Michelle" last="Buscarilli">Michelle Buscarilli</name>
<affiliation wicri:level="4"><nlm:affiliation>Unidade de Genética do Instituto da Criança-Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.</nlm:affiliation>
<country xml:lang="fr">Brésil</country>
<wicri:regionArea>Unidade de Genética do Instituto da Criança-Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo</wicri:regionArea>
<placeName><settlement type="city">São Paulo</settlement>
<region type="state">État de São Paulo</region>
<settlement type="city">São Paulo</settlement>
</placeName>
<orgName type="university">Université de São Paulo</orgName>
</affiliation>
</author>
<author><name sortKey="Dyack, Sarah" sort="Dyack, Sarah" uniqKey="Dyack S" first="Sarah" last="Dyack">Sarah Dyack</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Paediatrics and Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.</nlm:affiliation>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Department of Paediatrics and Medicine, Dalhousie University, Halifax, Nova Scotia</wicri:regionArea>
<wicri:noRegion>Nova Scotia</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Gillis, Jane" sort="Gillis, Jane" uniqKey="Gillis J" first="Jane" last="Gillis">Jane Gillis</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Pediatrics, University of British Columbia, Division of Biochemical Diseases, BC Children's Hospital, Vancouver, British Columbia, Canada.</nlm:affiliation>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Department of Pediatrics, University of British Columbia, Division of Biochemical Diseases, BC Children's Hospital, Vancouver, British Columbia</wicri:regionArea>
<wicri:noRegion>British Columbia</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Yntema, Helger G" sort="Yntema, Helger G" uniqKey="Yntema H" first="Helger G" last="Yntema">Helger G. Yntema</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.</nlm:affiliation>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Human Genetics, Radboud University Medical Center, Nijmegen</wicri:regionArea>
<placeName><settlement type="city">Nimègue</settlement>
<region type="province" nuts="2">Gueldre</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Pantaleoni, Francesca" sort="Pantaleoni, Francesca" uniqKey="Pantaleoni F" first="Francesca" last="Pantaleoni">Francesca Pantaleoni</name>
<affiliation wicri:level="3"><nlm:affiliation>Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, Rome, Italy.</nlm:affiliation>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, Rome</wicri:regionArea>
<placeName><settlement type="city">Rome</settlement>
<region nuts="2">Latium</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Van Loon, Rosa Le" sort="Van Loon, Rosa Le" uniqKey="Van Loon R" first="Rosa Le" last="Van Loon">Rosa Le Van Loon</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands.</nlm:affiliation>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Clinical Genetics, Erasmus Medical Center, Rotterdam</wicri:regionArea>
<placeName><settlement type="city">Rotterdam</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Mackay, Sara" sort="Mackay, Sara" uniqKey="Mackay S" first="Sara" last="Mackay">Sara Mackay</name>
<affiliation wicri:level="1"><nlm:affiliation>Maritime Medical Genetics Service, IWK Health Centre, Halifax, Nova Scotia, Canada.</nlm:affiliation>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Maritime Medical Genetics Service, IWK Health Centre, Halifax, Nova Scotia</wicri:regionArea>
<wicri:noRegion>Nova Scotia</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Mina, Kym" sort="Mina, Kym" uniqKey="Mina K" first="Kym" last="Mina">Kym Mina</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Diagnostic Genomics, PathWest Laboratory Medicine WA, Perth, Western Australia, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Diagnostic Genomics, PathWest Laboratory Medicine WA, Perth, Western Australia</wicri:regionArea>
<wicri:noRegion>Western Australia</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Schanze, Ina" sort="Schanze, Ina" uniqKey="Schanze I" first="Ina" last="Schanze">Ina Schanze</name>
<affiliation wicri:level="3"><nlm:affiliation>Institute of Human Genetics, University Hospital Magdeburg, Magdeburg, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institute of Human Genetics, University Hospital Magdeburg, Magdeburg</wicri:regionArea>
<placeName><region type="land" nuts="2">Saxe-Anhalt</region>
<settlement type="city">Magdebourg</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Tan, Tiong Yang" sort="Tan, Tiong Yang" uniqKey="Tan T" first="Tiong Yang" last="Tan">Tiong Yang Tan</name>
<affiliation wicri:level="1"><nlm:affiliation>Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, Victoria, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, Victoria</wicri:regionArea>
<wicri:noRegion>Victoria</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Walsh, Maie" sort="Walsh, Maie" uniqKey="Walsh M" first="Maie" last="Walsh">Maie Walsh</name>
<affiliation wicri:level="1"><nlm:affiliation>Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, Victoria, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, Victoria</wicri:regionArea>
<wicri:noRegion>Victoria</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="White, Susan M" sort="White, Susan M" uniqKey="White S" first="Susan M" last="White">Susan M. White</name>
<affiliation wicri:level="1"><nlm:affiliation>Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, Victoria, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, Victoria</wicri:regionArea>
<wicri:noRegion>Victoria</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Niewisch, Marena R" sort="Niewisch, Marena R" uniqKey="Niewisch M" first="Marena R" last="Niewisch">Marena R. Niewisch</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology and Oncology, Medical Center - University of Freiburg, Faculty of Medicine, Freiburg, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology and Oncology, Medical Center - University of Freiburg, Faculty of Medicine, Freiburg</wicri:regionArea>
<placeName><region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Fribourg-en-Brisgau</region>
<settlement type="city">Fribourg-en-Brisgau</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Garcia Mi Aur, Sixto" sort="Garcia Mi Aur, Sixto" uniqKey="Garcia Mi Aur S" first="Sixto" last="García-Mi Aúr">Sixto García-Mi Aúr</name>
<affiliation wicri:level="3"><nlm:affiliation>Instituto de Genética Médica y Molecular, Hospital Universitario La Paz, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Instituto de Genética Médica y Molecular, Hospital Universitario La Paz, Madrid</wicri:regionArea>
<placeName><settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Plaza, Diego" sort="Plaza, Diego" uniqKey="Plaza D" first="Diego" last="Plaza">Diego Plaza</name>
<affiliation wicri:level="3"><nlm:affiliation>Unidad de Hemato-Oncología Pediátrica, Hospital Universitario La Paz, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Unidad de Hemato-Oncología Pediátrica, Hospital Universitario La Paz, Madrid</wicri:regionArea>
<placeName><settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Ahmadian, Mohammad Reza" sort="Ahmadian, Mohammad Reza" uniqKey="Ahmadian M" first="Mohammad Reza" last="Ahmadian">Mohammad Reza Ahmadian</name>
<affiliation wicri:level="3"><nlm:affiliation>Institute of Biochemistry and Molecular Biology II, Medical Faculty of the Heinrich Heine University, Düsseldorf, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institute of Biochemistry and Molecular Biology II, Medical Faculty of the Heinrich Heine University, Düsseldorf</wicri:regionArea>
<placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
<region type="district" nuts="2">District de Düsseldorf</region>
<settlement type="city">Düsseldorf</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Cave, Helene" sort="Cave, Helene" uniqKey="Cave H" first="Hélène" last="Cavé">Hélène Cavé</name>
<affiliation wicri:level="3"><nlm:affiliation>INSERM UMR_S1131, Institut Universitaire d'Hématologie, Université Paris Diderot, Paris-Sorbonne-Cité, Paris, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>INSERM UMR_S1131, Institut Universitaire d'Hématologie, Université Paris Diderot, Paris-Sorbonne-Cité, Paris</wicri:regionArea>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Tartaglia, Marco" sort="Tartaglia, Marco" uniqKey="Tartaglia M" first="Marco" last="Tartaglia">Marco Tartaglia</name>
<affiliation wicri:level="3"><nlm:affiliation>Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, Rome, Italy.</nlm:affiliation>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, Rome</wicri:regionArea>
<placeName><settlement type="city">Rome</settlement>
<region nuts="2">Latium</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Zenker, Martin" sort="Zenker, Martin" uniqKey="Zenker M" first="Martin" last="Zenker">Martin Zenker</name>
<affiliation wicri:level="3"><nlm:affiliation>Institute of Human Genetics, University Hospital Magdeburg, Magdeburg, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institute of Human Genetics, University Hospital Magdeburg, Magdeburg</wicri:regionArea>
<placeName><region type="land" nuts="2">Saxe-Anhalt</region>
<settlement type="city">Magdebourg</settlement>
</placeName>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PubMed</idno>
<date when="2017">2017</date>
<idno type="RBID">pubmed:28594414</idno>
<idno type="pmid">28594414</idno>
<idno type="doi">10.1038/ejhg.2017.65</idno>
<idno type="wicri:Area/PubMed/Corpus">000A30</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000A30</idno>
<idno type="wicri:Area/PubMed/Curation">000A27</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000A27</idno>
<idno type="wicri:Area/PubMed/Checkpoint">000A27</idno>
<idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000A27</idno>
<idno type="wicri:Area/Ncbi/Merge">004943</idno>
<idno type="wicri:Area/Ncbi/Curation">004943</idno>
<idno type="wicri:Area/Ncbi/Checkpoint">004943</idno>
<idno type="wicri:Area/Main/Merge">000B47</idno>
<idno type="wicri:Area/Main/Curation">000B52</idno>
<idno type="wicri:Area/Main/Exploration">000B52</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en">Genotype and phenotype spectrum of NRAS germline variants.</title>
<author><name sortKey="Altmuller, Franziska" sort="Altmuller, Franziska" uniqKey="Altmuller F" first="Franziska" last="Altmüller">Franziska Altmüller</name>
<affiliation wicri:level="3"><nlm:affiliation>Institute of Human Genetics, University Hospital Magdeburg, Magdeburg, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institute of Human Genetics, University Hospital Magdeburg, Magdeburg</wicri:regionArea>
<placeName><region type="land" nuts="2">Saxe-Anhalt</region>
<settlement type="city">Magdebourg</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Lissewski, Christina" sort="Lissewski, Christina" uniqKey="Lissewski C" first="Christina" last="Lissewski">Christina Lissewski</name>
<affiliation wicri:level="3"><nlm:affiliation>Institute of Human Genetics, University Hospital Magdeburg, Magdeburg, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institute of Human Genetics, University Hospital Magdeburg, Magdeburg</wicri:regionArea>
<placeName><region type="land" nuts="2">Saxe-Anhalt</region>
<settlement type="city">Magdebourg</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Bertola, Debora" sort="Bertola, Debora" uniqKey="Bertola D" first="Debora" last="Bertola">Debora Bertola</name>
<affiliation wicri:level="4"><nlm:affiliation>Unidade de Genética do Instituto da Criança-Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.</nlm:affiliation>
<country xml:lang="fr">Brésil</country>
<wicri:regionArea>Unidade de Genética do Instituto da Criança-Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo</wicri:regionArea>
<placeName><settlement type="city">São Paulo</settlement>
<region type="state">État de São Paulo</region>
<settlement type="city">São Paulo</settlement>
</placeName>
<orgName type="university">Université de São Paulo</orgName>
</affiliation>
</author>
<author><name sortKey="Flex, Elisabetta" sort="Flex, Elisabetta" uniqKey="Flex E" first="Elisabetta" last="Flex">Elisabetta Flex</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.</nlm:affiliation>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome</wicri:regionArea>
<placeName><settlement type="city">Rome</settlement>
<region nuts="2">Latium</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Stark, Zornitza" sort="Stark, Zornitza" uniqKey="Stark Z" first="Zornitza" last="Stark">Zornitza Stark</name>
<affiliation wicri:level="3"><nlm:affiliation>Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne</wicri:regionArea>
<placeName><settlement type="city">Melbourne</settlement>
<region type="état">Victoria (État)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Spranger, Stephanie" sort="Spranger, Stephanie" uniqKey="Spranger S" first="Stephanie" last="Spranger">Stephanie Spranger</name>
<affiliation wicri:level="3"><nlm:affiliation>Praxis für Humangenetik, Bremen, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Praxis für Humangenetik, Bremen</wicri:regionArea>
<placeName><region type="land" nuts="3">Brême (Land)</region>
<settlement type="city">Brême</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Baynam, Gareth" sort="Baynam, Gareth" uniqKey="Baynam G" first="Gareth" last="Baynam">Gareth Baynam</name>
<affiliation wicri:level="1"><nlm:affiliation>Genetic Services of Western Australia, WA Department of Health, Perth, Western Australia, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Genetic Services of Western Australia, WA Department of Health, Perth, Western Australia</wicri:regionArea>
<wicri:noRegion>Western Australia</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Buscarilli, Michelle" sort="Buscarilli, Michelle" uniqKey="Buscarilli M" first="Michelle" last="Buscarilli">Michelle Buscarilli</name>
<affiliation wicri:level="4"><nlm:affiliation>Unidade de Genética do Instituto da Criança-Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.</nlm:affiliation>
<country xml:lang="fr">Brésil</country>
<wicri:regionArea>Unidade de Genética do Instituto da Criança-Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo</wicri:regionArea>
<placeName><settlement type="city">São Paulo</settlement>
<region type="state">État de São Paulo</region>
<settlement type="city">São Paulo</settlement>
</placeName>
<orgName type="university">Université de São Paulo</orgName>
</affiliation>
</author>
<author><name sortKey="Dyack, Sarah" sort="Dyack, Sarah" uniqKey="Dyack S" first="Sarah" last="Dyack">Sarah Dyack</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Paediatrics and Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.</nlm:affiliation>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Department of Paediatrics and Medicine, Dalhousie University, Halifax, Nova Scotia</wicri:regionArea>
<wicri:noRegion>Nova Scotia</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Gillis, Jane" sort="Gillis, Jane" uniqKey="Gillis J" first="Jane" last="Gillis">Jane Gillis</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Pediatrics, University of British Columbia, Division of Biochemical Diseases, BC Children's Hospital, Vancouver, British Columbia, Canada.</nlm:affiliation>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Department of Pediatrics, University of British Columbia, Division of Biochemical Diseases, BC Children's Hospital, Vancouver, British Columbia</wicri:regionArea>
<wicri:noRegion>British Columbia</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Yntema, Helger G" sort="Yntema, Helger G" uniqKey="Yntema H" first="Helger G" last="Yntema">Helger G. Yntema</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.</nlm:affiliation>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Human Genetics, Radboud University Medical Center, Nijmegen</wicri:regionArea>
<placeName><settlement type="city">Nimègue</settlement>
<region type="province" nuts="2">Gueldre</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Pantaleoni, Francesca" sort="Pantaleoni, Francesca" uniqKey="Pantaleoni F" first="Francesca" last="Pantaleoni">Francesca Pantaleoni</name>
<affiliation wicri:level="3"><nlm:affiliation>Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, Rome, Italy.</nlm:affiliation>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, Rome</wicri:regionArea>
<placeName><settlement type="city">Rome</settlement>
<region nuts="2">Latium</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Van Loon, Rosa Le" sort="Van Loon, Rosa Le" uniqKey="Van Loon R" first="Rosa Le" last="Van Loon">Rosa Le Van Loon</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands.</nlm:affiliation>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Clinical Genetics, Erasmus Medical Center, Rotterdam</wicri:regionArea>
<placeName><settlement type="city">Rotterdam</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Mackay, Sara" sort="Mackay, Sara" uniqKey="Mackay S" first="Sara" last="Mackay">Sara Mackay</name>
<affiliation wicri:level="1"><nlm:affiliation>Maritime Medical Genetics Service, IWK Health Centre, Halifax, Nova Scotia, Canada.</nlm:affiliation>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Maritime Medical Genetics Service, IWK Health Centre, Halifax, Nova Scotia</wicri:regionArea>
<wicri:noRegion>Nova Scotia</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Mina, Kym" sort="Mina, Kym" uniqKey="Mina K" first="Kym" last="Mina">Kym Mina</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Diagnostic Genomics, PathWest Laboratory Medicine WA, Perth, Western Australia, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Diagnostic Genomics, PathWest Laboratory Medicine WA, Perth, Western Australia</wicri:regionArea>
<wicri:noRegion>Western Australia</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Schanze, Ina" sort="Schanze, Ina" uniqKey="Schanze I" first="Ina" last="Schanze">Ina Schanze</name>
<affiliation wicri:level="3"><nlm:affiliation>Institute of Human Genetics, University Hospital Magdeburg, Magdeburg, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institute of Human Genetics, University Hospital Magdeburg, Magdeburg</wicri:regionArea>
<placeName><region type="land" nuts="2">Saxe-Anhalt</region>
<settlement type="city">Magdebourg</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Tan, Tiong Yang" sort="Tan, Tiong Yang" uniqKey="Tan T" first="Tiong Yang" last="Tan">Tiong Yang Tan</name>
<affiliation wicri:level="1"><nlm:affiliation>Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, Victoria, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, Victoria</wicri:regionArea>
<wicri:noRegion>Victoria</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Walsh, Maie" sort="Walsh, Maie" uniqKey="Walsh M" first="Maie" last="Walsh">Maie Walsh</name>
<affiliation wicri:level="1"><nlm:affiliation>Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, Victoria, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, Victoria</wicri:regionArea>
<wicri:noRegion>Victoria</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="White, Susan M" sort="White, Susan M" uniqKey="White S" first="Susan M" last="White">Susan M. White</name>
<affiliation wicri:level="1"><nlm:affiliation>Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, Victoria, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, Victoria</wicri:regionArea>
<wicri:noRegion>Victoria</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Niewisch, Marena R" sort="Niewisch, Marena R" uniqKey="Niewisch M" first="Marena R" last="Niewisch">Marena R. Niewisch</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology and Oncology, Medical Center - University of Freiburg, Faculty of Medicine, Freiburg, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology and Oncology, Medical Center - University of Freiburg, Faculty of Medicine, Freiburg</wicri:regionArea>
<placeName><region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Fribourg-en-Brisgau</region>
<settlement type="city">Fribourg-en-Brisgau</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Garcia Mi Aur, Sixto" sort="Garcia Mi Aur, Sixto" uniqKey="Garcia Mi Aur S" first="Sixto" last="García-Mi Aúr">Sixto García-Mi Aúr</name>
<affiliation wicri:level="3"><nlm:affiliation>Instituto de Genética Médica y Molecular, Hospital Universitario La Paz, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Instituto de Genética Médica y Molecular, Hospital Universitario La Paz, Madrid</wicri:regionArea>
<placeName><settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Plaza, Diego" sort="Plaza, Diego" uniqKey="Plaza D" first="Diego" last="Plaza">Diego Plaza</name>
<affiliation wicri:level="3"><nlm:affiliation>Unidad de Hemato-Oncología Pediátrica, Hospital Universitario La Paz, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Unidad de Hemato-Oncología Pediátrica, Hospital Universitario La Paz, Madrid</wicri:regionArea>
<placeName><settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Ahmadian, Mohammad Reza" sort="Ahmadian, Mohammad Reza" uniqKey="Ahmadian M" first="Mohammad Reza" last="Ahmadian">Mohammad Reza Ahmadian</name>
<affiliation wicri:level="3"><nlm:affiliation>Institute of Biochemistry and Molecular Biology II, Medical Faculty of the Heinrich Heine University, Düsseldorf, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institute of Biochemistry and Molecular Biology II, Medical Faculty of the Heinrich Heine University, Düsseldorf</wicri:regionArea>
<placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
<region type="district" nuts="2">District de Düsseldorf</region>
<settlement type="city">Düsseldorf</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Cave, Helene" sort="Cave, Helene" uniqKey="Cave H" first="Hélène" last="Cavé">Hélène Cavé</name>
<affiliation wicri:level="3"><nlm:affiliation>INSERM UMR_S1131, Institut Universitaire d'Hématologie, Université Paris Diderot, Paris-Sorbonne-Cité, Paris, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>INSERM UMR_S1131, Institut Universitaire d'Hématologie, Université Paris Diderot, Paris-Sorbonne-Cité, Paris</wicri:regionArea>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Tartaglia, Marco" sort="Tartaglia, Marco" uniqKey="Tartaglia M" first="Marco" last="Tartaglia">Marco Tartaglia</name>
<affiliation wicri:level="3"><nlm:affiliation>Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, Rome, Italy.</nlm:affiliation>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, Rome</wicri:regionArea>
<placeName><settlement type="city">Rome</settlement>
<region nuts="2">Latium</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Zenker, Martin" sort="Zenker, Martin" uniqKey="Zenker M" first="Martin" last="Zenker">Martin Zenker</name>
<affiliation wicri:level="3"><nlm:affiliation>Institute of Human Genetics, University Hospital Magdeburg, Magdeburg, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institute of Human Genetics, University Hospital Magdeburg, Magdeburg</wicri:regionArea>
<placeName><region type="land" nuts="2">Saxe-Anhalt</region>
<settlement type="city">Magdebourg</settlement>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j">European journal of human genetics : EJHG</title>
<idno type="eISSN">1476-5438</idno>
<imprint><date when="2017" type="published">2017</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adolescent</term>
<term>Adult</term>
<term>Child</term>
<term>Child, Preschool</term>
<term>Costello Syndrome (genetics)</term>
<term>Costello Syndrome (pathology)</term>
<term>Ectodermal Dysplasia (genetics)</term>
<term>Ectodermal Dysplasia (pathology)</term>
<term>Facies</term>
<term>Failure to Thrive (genetics)</term>
<term>Failure to Thrive (pathology)</term>
<term>Female</term>
<term>GTP Phosphohydrolases (genetics)</term>
<term>Genotype</term>
<term>Germ-Line Mutation</term>
<term>Heart Defects, Congenital (genetics)</term>
<term>Heart Defects, Congenital (pathology)</term>
<term>Humans</term>
<term>Infant</term>
<term>Infant, Newborn</term>
<term>Male</term>
<term>Membrane Proteins (genetics)</term>
<term>Mutation, Missense</term>
<term>Noonan Syndrome (genetics)</term>
<term>Noonan Syndrome (pathology)</term>
<term>Phenotype</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Adolescent</term>
<term>Adulte</term>
<term>Cardiopathies congénitales (anatomopathologie)</term>
<term>Cardiopathies congénitales (génétique)</term>
<term>Dysplasie ectodermique (anatomopathologie)</term>
<term>Dysplasie ectodermique (génétique)</term>
<term>Enfant</term>
<term>Enfant d'âge préscolaire</term>
<term>Faciès</term>
<term>Femelle</term>
<term>Génotype</term>
<term>Humains</term>
<term>Mutation faux-sens</term>
<term>Mutation germinale</term>
<term>Mâle</term>
<term>Nourrisson</term>
<term>Nouveau-né</term>
<term>Phénotype</term>
<term>Protéines membranaires (génétique)</term>
<term>Retard de croissance staturo-pondérale (anatomopathologie)</term>
<term>Retard de croissance staturo-pondérale (génétique)</term>
<term>Syndrome de Costello (anatomopathologie)</term>
<term>Syndrome de Costello (génétique)</term>
<term>Syndrome de Noonan (anatomopathologie)</term>
<term>Syndrome de Noonan (génétique)</term>
<term>dGTPases (génétique)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>GTP Phosphohydrolases</term>
<term>Membrane Proteins</term>
</keywords>
<keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Cardiopathies congénitales</term>
<term>Dysplasie ectodermique</term>
<term>Retard de croissance staturo-pondérale</term>
<term>Syndrome de Costello</term>
<term>Syndrome de Noonan</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Costello Syndrome</term>
<term>Ectodermal Dysplasia</term>
<term>Failure to Thrive</term>
<term>Heart Defects, Congenital</term>
<term>Noonan Syndrome</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Cardiopathies congénitales</term>
<term>Dysplasie ectodermique</term>
<term>Protéines membranaires</term>
<term>Retard de croissance staturo-pondérale</term>
<term>Syndrome de Costello</term>
<term>Syndrome de Noonan</term>
<term>dGTPases</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Costello Syndrome</term>
<term>Ectodermal Dysplasia</term>
<term>Failure to Thrive</term>
<term>Heart Defects, Congenital</term>
<term>Noonan Syndrome</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Adolescent</term>
<term>Adult</term>
<term>Child</term>
<term>Child, Preschool</term>
<term>Facies</term>
<term>Female</term>
<term>Genotype</term>
<term>Germ-Line Mutation</term>
<term>Humans</term>
<term>Infant</term>
<term>Infant, Newborn</term>
<term>Male</term>
<term>Mutation, Missense</term>
<term>Phenotype</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Adolescent</term>
<term>Adulte</term>
<term>Enfant</term>
<term>Enfant d'âge préscolaire</term>
<term>Faciès</term>
<term>Femelle</term>
<term>Génotype</term>
<term>Humains</term>
<term>Mutation faux-sens</term>
<term>Mutation germinale</term>
<term>Mâle</term>
<term>Nourrisson</term>
<term>Nouveau-né</term>
<term>Phénotype</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">RASopathies comprise a group of disorders clinically characterized by short stature, heart defects, facial dysmorphism, and varying degrees of intellectual disability and cancer predisposition. They are caused by germline variants in genes encoding key components or modulators of the highly conserved RAS-MAPK signalling pathway that lead to dysregulation of cell signal transmission. Germline changes in the genes encoding members of the RAS subfamily of GTPases are rare and associated with variable phenotypes of the RASopathy spectrum, ranging from Costello syndrome (HRAS variants) to Noonan and Cardiofaciocutaneous syndromes (KRAS variants). A small number of RASopathy cases with disease-causing germline NRAS alterations have been reported. Affected individuals exhibited features fitting Noonan syndrome, and the observed germline variants differed from the typical oncogenic NRAS changes occurring as somatic events in tumours. Here we describe 19 new cases with RASopathy due to disease-causing variants in NRAS. Importantly, four of them harbored missense changes affecting Gly12, which was previously described to occur exclusively in cancer. The phenotype in our cohort was variable but well within the RASopathy spectrum. Further, one of the patients (c.35G>A; p.(Gly12Asp)) had a myeloproliferative disorder, and one subject (c.34G>C; p.(Gly12Arg)) exhibited an uncharacterized brain tumour. With this report, we expand the genotype and phenotype spectrum of RASopathy-associated germline NRAS variants and provide evidence that NRAS variants do not spare the cancer-associated mutation hotspots.</div>
</front>
</TEI>
<affiliations><list><country><li>Allemagne</li>
<li>Australie</li>
<li>Brésil</li>
<li>Canada</li>
<li>Espagne</li>
<li>France</li>
<li>Italie</li>
<li>Pays-Bas</li>
</country>
<region><li>Bade-Wurtemberg</li>
<li>Brême (Land)</li>
<li>Communauté de Madrid</li>
<li>District de Düsseldorf</li>
<li>District de Fribourg-en-Brisgau</li>
<li>Gueldre</li>
<li>Hollande-Méridionale</li>
<li>Latium</li>
<li>Rhénanie-du-Nord-Westphalie</li>
<li>Saxe-Anhalt</li>
<li>Victoria (État)</li>
<li>État de São Paulo</li>
<li>Île-de-France</li>
</region>
<settlement><li>Brême</li>
<li>Düsseldorf</li>
<li>Fribourg-en-Brisgau</li>
<li>Madrid</li>
<li>Magdebourg</li>
<li>Melbourne</li>
<li>Nimègue</li>
<li>Paris</li>
<li>Rome</li>
<li>Rotterdam</li>
<li>São Paulo</li>
</settlement>
<orgName><li>Université de São Paulo</li>
</orgName>
</list>
<tree><country name="Allemagne"><region name="Saxe-Anhalt"><name sortKey="Altmuller, Franziska" sort="Altmuller, Franziska" uniqKey="Altmuller F" first="Franziska" last="Altmüller">Franziska Altmüller</name>
</region>
<name sortKey="Ahmadian, Mohammad Reza" sort="Ahmadian, Mohammad Reza" uniqKey="Ahmadian M" first="Mohammad Reza" last="Ahmadian">Mohammad Reza Ahmadian</name>
<name sortKey="Lissewski, Christina" sort="Lissewski, Christina" uniqKey="Lissewski C" first="Christina" last="Lissewski">Christina Lissewski</name>
<name sortKey="Niewisch, Marena R" sort="Niewisch, Marena R" uniqKey="Niewisch M" first="Marena R" last="Niewisch">Marena R. Niewisch</name>
<name sortKey="Schanze, Ina" sort="Schanze, Ina" uniqKey="Schanze I" first="Ina" last="Schanze">Ina Schanze</name>
<name sortKey="Spranger, Stephanie" sort="Spranger, Stephanie" uniqKey="Spranger S" first="Stephanie" last="Spranger">Stephanie Spranger</name>
<name sortKey="Zenker, Martin" sort="Zenker, Martin" uniqKey="Zenker M" first="Martin" last="Zenker">Martin Zenker</name>
</country>
<country name="Brésil"><region name="État de São Paulo"><name sortKey="Bertola, Debora" sort="Bertola, Debora" uniqKey="Bertola D" first="Debora" last="Bertola">Debora Bertola</name>
</region>
<name sortKey="Buscarilli, Michelle" sort="Buscarilli, Michelle" uniqKey="Buscarilli M" first="Michelle" last="Buscarilli">Michelle Buscarilli</name>
</country>
<country name="Italie"><region name="Latium"><name sortKey="Flex, Elisabetta" sort="Flex, Elisabetta" uniqKey="Flex E" first="Elisabetta" last="Flex">Elisabetta Flex</name>
</region>
<name sortKey="Pantaleoni, Francesca" sort="Pantaleoni, Francesca" uniqKey="Pantaleoni F" first="Francesca" last="Pantaleoni">Francesca Pantaleoni</name>
<name sortKey="Tartaglia, Marco" sort="Tartaglia, Marco" uniqKey="Tartaglia M" first="Marco" last="Tartaglia">Marco Tartaglia</name>
</country>
<country name="Australie"><region name="Victoria (État)"><name sortKey="Stark, Zornitza" sort="Stark, Zornitza" uniqKey="Stark Z" first="Zornitza" last="Stark">Zornitza Stark</name>
</region>
<name sortKey="Baynam, Gareth" sort="Baynam, Gareth" uniqKey="Baynam G" first="Gareth" last="Baynam">Gareth Baynam</name>
<name sortKey="Mina, Kym" sort="Mina, Kym" uniqKey="Mina K" first="Kym" last="Mina">Kym Mina</name>
<name sortKey="Tan, Tiong Yang" sort="Tan, Tiong Yang" uniqKey="Tan T" first="Tiong Yang" last="Tan">Tiong Yang Tan</name>
<name sortKey="Walsh, Maie" sort="Walsh, Maie" uniqKey="Walsh M" first="Maie" last="Walsh">Maie Walsh</name>
<name sortKey="White, Susan M" sort="White, Susan M" uniqKey="White S" first="Susan M" last="White">Susan M. White</name>
</country>
<country name="Canada"><noRegion><name sortKey="Dyack, Sarah" sort="Dyack, Sarah" uniqKey="Dyack S" first="Sarah" last="Dyack">Sarah Dyack</name>
</noRegion>
<name sortKey="Gillis, Jane" sort="Gillis, Jane" uniqKey="Gillis J" first="Jane" last="Gillis">Jane Gillis</name>
<name sortKey="Mackay, Sara" sort="Mackay, Sara" uniqKey="Mackay S" first="Sara" last="Mackay">Sara Mackay</name>
</country>
<country name="Pays-Bas"><region name="Gueldre"><name sortKey="Yntema, Helger G" sort="Yntema, Helger G" uniqKey="Yntema H" first="Helger G" last="Yntema">Helger G. Yntema</name>
</region>
<name sortKey="Van Loon, Rosa Le" sort="Van Loon, Rosa Le" uniqKey="Van Loon R" first="Rosa Le" last="Van Loon">Rosa Le Van Loon</name>
</country>
<country name="Espagne"><region name="Communauté de Madrid"><name sortKey="Garcia Mi Aur, Sixto" sort="Garcia Mi Aur, Sixto" uniqKey="Garcia Mi Aur S" first="Sixto" last="García-Mi Aúr">Sixto García-Mi Aúr</name>
</region>
<name sortKey="Plaza, Diego" sort="Plaza, Diego" uniqKey="Plaza D" first="Diego" last="Plaza">Diego Plaza</name>
</country>
<country name="France"><region name="Île-de-France"><name sortKey="Cave, Helene" sort="Cave, Helene" uniqKey="Cave H" first="Hélène" last="Cavé">Hélène Cavé</name>
</region>
</country>
</tree>
</affiliations>
</record>

Pour manipuler ce document sous Unix (Dilib)

EXPLOR_STEP=$WICRI_ROOT/Wicri/Asie/explor/AustralieFrV1/Data/Main/Exploration

HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000B52 | SxmlIndent | more

HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 000B52 | SxmlIndent | more

Pour mettre un lien sur cette page dans le réseau Wicri

{{Explor lien
   |wiki=    Wicri/Asie
   |area=    AustralieFrV1
   |flux=    Main
   |étape=   Exploration
   |type=    RBID
   |clé=     pubmed:28594414
   |texte=   Genotype and phenotype spectrum of NRAS germline variants.
}}

Pour générer des pages wiki

HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i   -Sk "pubmed:28594414" \
       | HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd   \
       | NlmPubMed2Wicri -a AustralieFrV1

This area was generated with Dilib version V0.6.33.
Data generation: Tue Dec 5 10:43:12 2017. Site generation: Tue Mar 5 14:07:20 2024

Serveur d'exploration sur les relations entre la France et l'Australie

Genotype and phenotype spectrum of NRAS germline variants.

Genotype and phenotype spectrum of NRAS germline variants.

Source :

Descripteurs français

English descriptors

Abstract

Links toward previous steps (curation, corpus...)

Le document en format XML

Pour manipuler ce document sous Unix (Dilib)

Pour mettre un lien sur cette page dans le réseau Wicri

Pour générer des pages wiki

	Serveur d'exploration sur les relations entre la France et l'Australie
	Attention, ce site est en cours de développement ! Attention, site généré par des moyens informatiques à partir de corpus bruts. Les informations ne sont donc pas validées.