ArticleHuman mutation2015
High Incidence of Noonan Syndrome Features Including Short Stature and Pulmonic Stenosis in Patients carrying NF1 Missense Mutations Affecting p.Arg1809: Genotype-Phenotype Correlation.
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Article in Human mutation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers, 1 of them a synthesis that pooled it.
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104citing papers in PubMed, 1 pooled it
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104 citing papers in PubMed, 1 synthesis or guideline pooled it.
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- Diagnoses of double heterozygous NF1 variants and dual RASopathy.Molecular and cellular pediatrics · 2026Review
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- Subtype distribution, clinical presentation, and molecular spectrum of neurofibromatosis type 1-associated breast cancer.Breast (Edinburgh, Scotland) · 2025Article
- The spectrum of pathogenic NF1 variants in participants enrolling on clinical trials of MEK inhibitors for plexiform neurofibroma.Human genetics · 2025Article
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- Comparison of rule- and large language model-based phenotype extraction from clinical notes for neurofibromatosis type 1.Journal of the American Medical Informatics Association : JAMIA · 2025Article
- Clinical and Genetic Characterization of Noonan Syndrome in a Romanian Cohort from Transylvania: Details onDiagnostics (Basel, Switzerland) · 2025Article
- Current states in understanding oligodendroglia-mediated neurological issues in neurofibromatosis type 1 (NF1).Acta neuropathologica communications · 2025Review
- Unraveling novel variants in the NF1 gene and investigating potential therapeutic strategies.Scientific reports · 2025Article
- Genetics and current research models of Mendelian tumor predisposition syndromes with ocular involvement.Progress in retinal and eye research · 2025Review
- Neurofibromatosis-Noonan syndrome: a prospective monocentric study of 26 patients and literature review.Orphanet journal of rare diseases · 2025Review
- Global proteomics and affinity mass spectrometry analysis of human Schwann cells indicates that variation in and loss of neurofibromin (NF1) alters protein expression and cellular and mitochondrial metabolism.Scientific reports · 2025Article
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- The genetic spectrum ofNeurosciences (Riyadh, Saudi Arabia) · 2024Article
44 more citing papers are in PubMed but not listed here.
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Authors and funding
73 authors.
Kitiwan RojnueangnitDepartment of Genetics, Medical Genomics Laboratory, University of Alabama at Birmingham, Birmingham, Alabama.
Jing XieDepartment of Genetics, Medical Genomics Laboratory, University of Alabama at Birmingham, Birmingham, Alabama.
Alicia GomesDepartment of Genetics, Medical Genomics Laboratory, University of Alabama at Birmingham, Birmingham, Alabama.
Angela SharpDepartment of Genetics, Medical Genomics Laboratory, University of Alabama at Birmingham, Birmingham, Alabama.
Tom CallensDepartment of Genetics, Medical Genomics Laboratory, University of Alabama at Birmingham, Birmingham, Alabama.
Yunjia ChenDepartment of Genetics, Medical Genomics Laboratory, University of Alabama at Birmingham, Birmingham, Alabama.
Ying LiuDepartment of Genetics, Medical Genomics Laboratory, University of Alabama at Birmingham, Birmingham, Alabama.
Meagan CochranDepartment of Genetics, Medical Genomics Laboratory, University of Alabama at Birmingham, Birmingham, Alabama.
Mary-Alice AbbottDepartment of Pediatrics, Tufts University School of Medicine, Springfield, Massachusetts.
Joan AtkinSection of Molecular and Human Genetics, Nationwide Children's Hospital, Columbus, Ohio.
Dusica Babovic-VuksanovicMedical Genetics, Mayo Clinic College of Medicine, Rochester, Minnesota.
Christopher P BarnettPediatric and Reproductive Genetics, SA Clinical Genetics Service, Women's and Children's Hospital/SA Pathology, North Adelaide, South Australia and Discipline of Pediatrics, University of Adelaide, Adelaide, Australia.
Melissa CrenshawDepartment of Clinical Genetics, All Children's Hospital, John Hopkins Medicine and Department of Pediatrics, John Hopkins University School of Medicine, Baltimore, Maryland.
Dennis W BartholomewSection of Molecular and Human Genetics, Nationwide Children's Hospital, Columbus, Ohio.
Lina BaselRaphael Recanati Genetics Institute, Beilinson Campus and Schneider Children's Medical Center of Israel/Felsenstein Medical Research Center, Rabin Medical Center, Petach Tikva, Israel and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Gary BellusDepartment of Clinical Genetics and Metabolism, Children's Hospital, University of Colorado, Denver-Aurora, Colorado.
Shay Ben-ShacharThe Genetic Institute, Tel-Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel-Aviv, Israel.
Martin G BialerDepartment of Pediatrics, North Shore LIJ Health System, Manhasset, New York.
David BickSection of Genetics, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin.
Bruce BlumbergKaiser Permanente Oakland, Oakland, California.
Fanny CortesCenter for Rare Diseases, Clinica Las Condes, Santiago, Chile.
Karen L DavidDepartment of Medicine, Division of Genetics, New York Methodist Hospital, Brooklyn, New York.
Anne DestreeInstitute of Pathology and Genetics (IPG), Gosselies, Belgium.
Anna Duat-RodriguezDepartment of Neuropediatrics, Hospital Infantil Universitario Niño Jesús, Madrid, Spain.
Dawn EarlDepartment of Pediatrics, Division of Genetic Medicine, University of Washington, and Seattle Children's Hospital, Seattle, Washington.
Luis EscobarMedical Genetics and Neurodevelopment Center, St Vincent Children's Hospital, Indianapolis, Indiana.
Marthanda EswaraSutter Memorial Hospital, Sacramento, California.
Begona EzquietaDepartment of Biochemistry, Hospital Universitario Gregorio Marañón, Institute of Health Research (IiSGM), Madrid, Spain.
Ian M FraylingInstitute of Medical Genetics, University Hospital of Wales, Cardiff, UK.
Moshe FrydmanChaim Sheba Medical Center, Tel Hashomer, Israel.
Kathy GardnerDepartment of Neurology, Veterans Administration Hospital of Pittsburgh and University of Pittsburgh, Pittsburgh, Pennsylvania.
Karen W GrippDivision of Medical Genetics, AI duPont Hospital for Children, Wilmington, Delaware.
Concepcion Hernández-ChicoDepartment of Genetics, Hospital Universitario Ramón y Cajal, Institute of Health Research (IRYCIS). Center for Biomedical Research-Network of Rare Diseases (CIBERER), Madrid, Spain.
Kurt HeyrmanChildren's Health Center-Pediatrics, Appleton, Wisconsin.
Jennifer IbrahimSt. Joseph's Children's Hospital, Paterson, New Jersey.
Sandra JanssensCenter for Medical Genetics, Ghent University Hospital, Gent, Belgium.
Beth A KeenaDivision of Human Genetics, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.
Isabel Llano-RivasDepartment of Genetics, Hospital Universitario Cruces, BioCruces Health Research Institute, Biscay, Spain.
Kathy LeppigGenetic Services, Group Health Cooperative and Department of Pathology, University of Washington, Seattle, Washington.
Marie McDonaldDepartment of Pediatrics, Division of Medical Genetics, Duke University Medical Center, Durham, North Carolina.
Vinod K MisraDepartment of Pediatrics, Division of Genetics and Metabolic Disorders, The Wayne State University School of Medicine, Detroit, Michigan.
Jennifer MulburyDepartment of Pediatrics and Neurology, University of Rochester Medical center, Rochester, New York.
Vinodh NarayananDorrance Center for Rare Childhood Disorders, Translational Genomics Research Institute (TGen), Phoenix, Arizona.
Naama OrensteinGenetics Unit, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.
Patricia Galvin-PartonStony Brook Children's, Stony Brook Medicine, Stony Brook, New York.
Helio PedroMedical Genetics, Hackensack University Medical Center, Hackensack, New Jersey.
Eniko K PivnickDepartment of Pediatrics, Division of Medical Genetics and Department of Ophthalmology University of Tennessee Health Science Center and Le Bonheur Children's Hospita l, Memphis, Tennessee.
Cynthia M PowellDepartment of Pediatrics, University of North Carolina, Chapel Hill, North Carolina.
Linda RandolphDivision of Medical Genetics, Children's Hospital Los Angeles, Los Angeles, California.
Salmo RaskinGroup for Advanced Molecular Investigation (NIMA), School of Health and Biosciences, Pontificia Universidade Catolica do Parana (PUCPR), Curibita, Brasil.
Jordi RosellGenetics Service, Hospital Son Espases, Palma de Mallorca, Spain.
Karol RubinUniversity of Minnesota Children's Hospital, Minneapolis, Minnesota.
Margretta SeashoreDepartment of Pediatrics and Genetics, Yale School of Medicine, New Haven, Connecticut.
Christian P SchaafDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.
Angela ScheuerleDepartment of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas.
Meredith SchultzNationwide Children's Hospital, Columbus, Ohio.
Elizabeth SchorryDepartment of Pediatrics, University of Cincinnati, Cincinnati, Ohio.
Rhonda SchnurDivision of Genetics, Cooper Medical School of Rowan University, Camden, New Jersey.
Elizabeth SiqvelandChildren's Hospitals and Clinics of Minnesota, Minneapolis, Minnesota.
Amanda TkachukDepartment of Clinical Genetics and Metabolism, Children's Hospital, University of Colorado, Denver-Aurora, Colorado.
James TonsgardDepartments of Pediatrics and Neurology, University of Chicago/Pritzker School of Medicine, Chicago, Illinois.
Meena UpadhyayaInstitute of Medical Genetics, University Hospital of Wales, Cardiff, UK.
Ishwar C VermaDepartment of Genetic Medicine, Sri Ganga Ram Hospital, New Delhi, India.
Stephanie WallaceDepartment of Pediatrics, Division of Genetic Medicine, University of Washington, and Seattle Children's Hospital, Seattle, Washington.
Charles WilliamsDepartment of Pediatrics, Division of Genetics and Metabolism, University of Florida, Gainesville, Florida.
Elaine ZackaiDivision of Human Genetics, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.
Jonathan ZonanaDepartments of Pediatrics and Molecular and Medical Genetics, Oregon Health and Science University, Portland, Oregon.
Conxi LazaroMolecular Diagnostics Unit, Hereditary Cancer Program, Catalan Institute of Oncology (ICO-IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
Kathleen ClaesCenter for Medical Genetics, Ghent University Hospital, Gent, Belgium.
Bruce KorfDepartment of Genetics, Medical Genomics Laboratory, University of Alabama at Birmingham, Birmingham, Alabama.
Yolanda MartinDepartment of Genetics, Hospital Universitario Ramón y Cajal, Institute of Health Research (IRYCIS). Center for Biomedical Research-Network of Rare Diseases (CIBERER), Madrid, Spain.
Eric LegiusDepartment of Human Genetics, KU Leuven, Leuven, Belgium.
Ludwine MessiaenDepartment of Genetics, Medical Genomics Laboratory, University of Alabama at Birmingham, Birmingham, Alabama.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neurofibromatosis type 1 (NF1) is one of the most frequent genetic disorders, affecting 1:3,000 worldwide. Identification of genotype-phenotype correlations is challenging because of the wide range clinical variability, the progressive nature of the disorder, and extreme diversity of the mutational spectrum. We report 136 individuals with a distinct phenotype carrying one of five different NF1 missense mutations affecting p.Arg1809. Patients presented with multiple café-au-lait macules (CALM) with or without freckling and Lisch nodules, but no externally visible plexiform neurofibromas or clear cutaneous neurofibromas were found. About 25% of the individuals had Noonan-like features. Pulmonic stenosis and short stature were significantly more prevalent compared with classic cohorts (P < 0.0001). Developmental delays and/or learning disabilities were reported in over 50% of patients. Melanocytes cultured from a CALM in a segmental NF1-patient showed two different somatic NF1 mutations, p.Arg1809Cys and a multi-exon deletion, providing genetic evidence that p.Arg1809Cys is a loss-of-function mutation in the melanocytes and causes a pigmentary phenotype. Constitutional missense mutations at p.Arg1809 affect 1.23% of unrelated NF1 probands in the UAB cohort, therefore this specific NF1 genotype-phenotype correlation will affect counseling and management of a significant number of patients.
Indexed as
Amino Acid SubstitutionCodonMutation, MissensePhenotypeAdolescentAdultChildChild, PreschoolCohort StudiesDwarfismFemaleGenetic Association StudiesHumansInfantMaleMiddle AgedCodonNeurofibromin 1Legius syndromeneurofibromatosis type 1NF1p.Arg1809phenotype-genotype correlations
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