The seventh international RASopathies symposium: Pathways to a cure-expanding knowledge, enhancing research, and therapeutic discovery

Maria I Kontaridis^{1

2

3}, Amy E Roberts^{4

5}, Lisa Schill⁶, Lisa Schoyer⁶, Beth Stronach⁶, Gregor Andelfinger⁷, Yoko Aoki⁸, Marni E Axelrad⁹, Annette Bakker¹⁰, Anton M Bennett¹¹, Alberto Broniscer¹², Pau Castel¹³, Caitlin A Chang¹⁴, Lukas Cyganek¹⁵, Tirtha K Das¹⁶, Jeroen den Hertog^{17

18}, Emilia Galperin¹⁹, Shruti Garg²⁰, Bruce D Gelb²¹, Kristiana Gordon²², Tamar Green²³, Karen W Gripp²⁴, Maxim Itkin²⁵, Maija Kiuru²⁶, Bruce R Korf²⁷, Jeff R Livingstone²⁸, Alejandro López-Juárez²⁹, Pilar L Magoulas³⁰, Sahar Mansour^{31

32}, Theresa Milner³³, Elisabeth Parker⁶, Elizabeth I Pierpont³⁴, Kevin Plouffe³⁵, Katherine A Rauen³⁶, Suma P Shankar^{36

37}, Shane B Smith³⁸, David A Stevenson³⁹, Marco Tartaglia⁴⁰, Richard Van⁴¹, Morgan E Wagner⁴², Stephanie M Ware⁴³, Martin Zenker⁴⁴

Affiliations

¹ Department of Biomedical Research and Translational Medicine, Masonic Medical Research Institute, Utica, New York, USA.
² Division of Cardiology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
³ Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, USA.
⁴ Department of Cardiology, Boston Children's Hospital, Boston, Massachusetts, USA.
⁵ Division of Genetics, Department of Pediatrics, Boston Children's Hospital, Boston, Massachusetts, USA.
⁶ RASopathies Network USA, Altadena, California, USA.
⁷ Cardiovascular Genetics, Department of Pediatrics, Centre Hospitalier Universitaire Saint-Justine Research Centre, Université de Montréal, Montréal, Canada.
⁸ Department of Medical Genetics, Tohoku University School of Medicine, Sendai, Japan.
⁹ Section of Psychology, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
¹⁰ Children's Tumor Foundation, New York, New York, USA.
¹¹ Yale Center for Molecular and Systems Metabolism, Yale University School of Medicine, New Haven, Connecticut, USA.
¹² Division of Hematology-Oncology, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA.
¹³ Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, New York, USA.
¹⁴ Department of Medical Genetics, BC Women and Children's Hospital, Vancouver, British Columbia, Canada.
¹⁵ Stem Cell Unit, Clinic for Cardiology and Pneumology, University Medical Center Göttingen, Göttingen, Germany.
¹⁶ Department of Cell, Developmental, and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
¹⁷ Hubrecht Institute-KNAW and University Medical Center Utrecht, Utrecht, The Netherlands.
¹⁸ Institute Biology Leiden, Leiden University, Leiden, The Netherlands.
¹⁹ Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, Kentucky, USA.
²⁰ Division of Neuroscience & Experimental Psychology, Faculty of Biology, Medicine and Health, School of Biological Sciences, Royal Manchester Children's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Sciences Centre, University of Manchester & Child & Adolescent Mental Health Services, Manchester, UK.
²¹ Mindich Child Health and Development Institute and the Departments of Pediatrics and Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
²² Lymphovascular Medicine, Dermatology Department, St. George's University, London, UK.
²³ Division of Interdisciplinary Brain Sciences, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California, USA.
²⁴ Department of Genetics, AI duPont Hospital for Children, Wilmington, Delaware, USA.
²⁵ Center for Lymphatic Disorders, Department of Radiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
²⁶ Department of Dermatology, Department of Pathology & Laboratory Medicine, University of California Davis, Sacramento, California, USA.
²⁷ Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama, USA.
²⁸ Igia Pharmaceuticals, Florence, Kentucky, USA.
²⁹ Department of Health and Biomedical Sciences, University of Texas Rio Grande Valley, Texas, USA.
³⁰ Department of Molecular and Human Genetics, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas, USA.
³¹ Molecular and Clinical Sciences Institute, St George's University, London, UK.
³² South West Thames Regional Genetics Service, St George's NHS Foundation Trust, London, UK.
³³ CFC International, Stafford, Virginia, USA.
³⁴ Division of Clinical Behavioral Neuroscience, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA.
³⁵ RASopathies Network, Ottawa, Ontario, Canada.
³⁶ Department of Pediatrics, Division of Genomic Medicine, MIND Institute, University of California Davis, Sacramento, California, USA.
³⁷ Department of Ophthalmology and Vision Science, School of Medicine, University of California Davis, Sacramento, California, USA.
³⁸ Neurofibromatosis Network, Orlando, Florida, USA.
³⁹ Department of Pediatrics, Division of Medical Genetics, Stanford University, Stanford, California, USA.
⁴⁰ Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, Italy.
⁴¹ Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California, USA.
⁴² NCI RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
⁴³ Department of Pediatrics, Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
⁴⁴ Institute of Human Genetics, University Hospital, Otto-von-Guericke University, Magdeburg, Germany.

PMID: 35266292
PMCID: PMC9117434
DOI: 10.1002/ajmg.a.62716

The seventh international RASopathies symposium: Pathways to a cure-expanding knowledge, enhancing research, and therapeutic discovery

Maria I Kontaridis et al. Am J Med Genet A. 2022 Jun.

. 2022 Jun;188(6):1915-1927.

doi: 10.1002/ajmg.a.62716. Epub 2022 Mar 9.

Authors

Affiliations

¹ Department of Biomedical Research and Translational Medicine, Masonic Medical Research Institute, Utica, New York, USA.
² Division of Cardiology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
³ Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, USA.
⁴ Department of Cardiology, Boston Children's Hospital, Boston, Massachusetts, USA.
⁵ Division of Genetics, Department of Pediatrics, Boston Children's Hospital, Boston, Massachusetts, USA.
⁶ RASopathies Network USA, Altadena, California, USA.
⁷ Cardiovascular Genetics, Department of Pediatrics, Centre Hospitalier Universitaire Saint-Justine Research Centre, Université de Montréal, Montréal, Canada.
⁸ Department of Medical Genetics, Tohoku University School of Medicine, Sendai, Japan.
⁹ Section of Psychology, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
¹⁰ Children's Tumor Foundation, New York, New York, USA.
¹¹ Yale Center for Molecular and Systems Metabolism, Yale University School of Medicine, New Haven, Connecticut, USA.
¹² Division of Hematology-Oncology, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA.
¹³ Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, New York, USA.
¹⁴ Department of Medical Genetics, BC Women and Children's Hospital, Vancouver, British Columbia, Canada.
¹⁵ Stem Cell Unit, Clinic for Cardiology and Pneumology, University Medical Center Göttingen, Göttingen, Germany.
¹⁶ Department of Cell, Developmental, and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
¹⁷ Hubrecht Institute-KNAW and University Medical Center Utrecht, Utrecht, The Netherlands.
¹⁸ Institute Biology Leiden, Leiden University, Leiden, The Netherlands.
¹⁹ Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, Kentucky, USA.
²⁰ Division of Neuroscience & Experimental Psychology, Faculty of Biology, Medicine and Health, School of Biological Sciences, Royal Manchester Children's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Sciences Centre, University of Manchester & Child & Adolescent Mental Health Services, Manchester, UK.
²¹ Mindich Child Health and Development Institute and the Departments of Pediatrics and Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
²² Lymphovascular Medicine, Dermatology Department, St. George's University, London, UK.
²³ Division of Interdisciplinary Brain Sciences, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California, USA.
²⁴ Department of Genetics, AI duPont Hospital for Children, Wilmington, Delaware, USA.
²⁵ Center for Lymphatic Disorders, Department of Radiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
²⁶ Department of Dermatology, Department of Pathology & Laboratory Medicine, University of California Davis, Sacramento, California, USA.
²⁷ Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama, USA.
²⁸ Igia Pharmaceuticals, Florence, Kentucky, USA.
²⁹ Department of Health and Biomedical Sciences, University of Texas Rio Grande Valley, Texas, USA.
³⁰ Department of Molecular and Human Genetics, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas, USA.
³¹ Molecular and Clinical Sciences Institute, St George's University, London, UK.
³² South West Thames Regional Genetics Service, St George's NHS Foundation Trust, London, UK.
³³ CFC International, Stafford, Virginia, USA.
³⁴ Division of Clinical Behavioral Neuroscience, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA.
³⁵ RASopathies Network, Ottawa, Ontario, Canada.
³⁶ Department of Pediatrics, Division of Genomic Medicine, MIND Institute, University of California Davis, Sacramento, California, USA.
³⁷ Department of Ophthalmology and Vision Science, School of Medicine, University of California Davis, Sacramento, California, USA.
³⁸ Neurofibromatosis Network, Orlando, Florida, USA.
³⁹ Department of Pediatrics, Division of Medical Genetics, Stanford University, Stanford, California, USA.
⁴⁰ Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, Italy.
⁴¹ Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California, USA.
⁴² NCI RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
⁴³ Department of Pediatrics, Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
⁴⁴ Institute of Human Genetics, University Hospital, Otto-von-Guericke University, Magdeburg, Germany.

PMID: 35266292
PMCID: PMC9117434
DOI: 10.1002/ajmg.a.62716

Abstract

RASopathies are a group of genetic disorders that are caused by genes that affect the canonical Ras/mitogen-activated protein kinase (MAPK) signaling pathway. Despite tremendous progress in understanding the molecular consequences of these genetic anomalies, little movement has been made in translating these findings to the clinic. This year, the seventh International RASopathies Symposium focused on expanding the research knowledge that we have gained over the years to enhance new discoveries in the field, ones that we hope can lead to effective therapeutic treatments. Indeed, for the first time, research efforts are finally being translated to the clinic, with compassionate use of Ras/MAPK pathway inhibitors for the treatment of RASopathies. This biannual meeting, organized by the RASopathies Network, brought together basic scientists, clinicians, clinician scientists, patients, advocates, and their families, as well as representatives from pharmaceutical companies and the National Institutes of Health. A history of RASopathy gene discovery, identification of new disease genes, and the latest research, both at the bench and in the clinic, were discussed.

Keywords: Costello syndrome; Noonan syndrome; RASopathy; cardiofaciocutaneus syndrome; neurofibromatosis; signaling.

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References

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The seventh international RASopathies symposium: Pathways to a cure-expanding knowledge, enhancing research, and therapeutic discovery

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The seventh international RASopathies symposium: Pathways to a cure-expanding knowledge, enhancing research, and therapeutic discovery

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