ArticleAmerican journal of human genetics2018
Genotype-Phenotype Correlation in NF1: Evidence for a More Severe Phenotype Associated with Missense Mutations Affecting NF1 Codons 844-848.
Open access · bronzeAbstract read
In one paragraph
Article in American journal of human genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 129 papers.
0numbers the graph read from it
0cells of the map it votes in
129citing papers in PubMed
10.0field-weighted citation impact, top 1% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
129 citing papers in PubMed, 205 citations in OpenAlex.
- ReNeu: A Pivotal, Phase IIb Trial of Mirdametinib in Adults and Children With Symptomatic Neurofibromatosis Type 1-Associated Plexiform Neurofibroma.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025Trial
- A coordinated shift toward a macrocytic and hypochromic erythrocyte phenotype in adults with neurofibromatosis type 1.JID innovations : skin science from molecules to population health · 2026Article
- Harmonizing Multi-Institutional Clinical Documentation Using Natural Language Processing in Neurofibromatosis Type 1.Neurology. Clinical practice · 2026Observational
- Relation Between Genotype and Behavioral Phenotype in Children and Adolescents With Neurofibromatosis Type 1.JAACAP open · 2026Article
- Management of plexiform neurofibromas in neurofibromatosis type 1: An Italian Delphi consensus.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Article
- Clinical characteristics and treatment strategies of brainstem lesion in children with neurofibromatosis type 1.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2026Article
- Article
- Café-au-lait macules in a cohort of Greek children genetically diagnosed with neurofibromatosis type 1: Prognostic significance beyond their diagnostic relevance.Dermatology online journal · 2026Article
- Resolving variants of uncertain significance in neurofibromatosis: An integrated approach combining deep learning and minigene assays.Functional & integrative genomics · 2026Article
- Article
- MEK inhibitors for neurofibromatosis type 1-associated central and peripheral nervous system tumors.Neuro-oncology advances · 2026Review
- Genetic and non-genetic factors influencing phenotypic variability in neurofibromatosis type 1.Orphanet journal of rare diseases · 2026Review
- Article
- Cerebrovascular Malformations Associated With Hereditary Hemorrhagic Telangiectasia and HHT-Like Syndromes: A Comparative Overview.European journal of neurology · 2026Review
- Preimplantation genetic testing for neurofibromatosis type 1: molecular genetic aspects and impact on reproductive counseling.Human reproduction (Oxford, England) · 2026Observational
- Systemic skewing of peripheral blood leukocyte composition in neurofibromatosis type 1.Frontiers in immunology · 2026Article
- Whole-genome sequencing in Brazilian patients with neurofibromatosis type 1, including novel variants, incidental findings, and dual diagnoses.Einstein (Sao Paulo, Brazil) · 2026Article
- Protein domain-specific genotype-phenotype correlation study of neurofibromatosis type 1.Scientific reports · 2025Article
- 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
69 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
75 authors at 20 institutions in 12 countries.
Magdalena KoczkowskaDepartment of Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Yunjia ChenDepartment of Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Tom CallensDepartment of Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Alicia GomesDepartment of Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Angela SharpDepartment of Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Sherrell JohnsonDepartment of Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Meng-Chang HsiaoDepartment of Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Zhenbin ChenDepartment of Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Meena BalasubramanianSheffield Clinical Genetics Service, Sheffield Children's NHS Foundation Trust, Sheffield S10 2TH, UK.
Christopher P BarnettWomen's and Children's Hospital/SA Pathology, North Adelaide, SA 5006, Australia.
Troy A BeckerMedical Genetics, John Hopkins All Children's Hospital, St. Petersburg, FL 33701, USA.
Shay Ben-ShacharThe Genetic Institute, Tel-Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel-Aviv 6997801, Israel.
Debora R BertolaDepartment of Pediatrics, University of São Paulo, São Paulo 05403-000, Brazil.
Jaishri O BlakeleyDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Emma M M Burkitt-WrightGenomic Medicine, Division of Evolution and Genomic Sciences, Manchester Academic Health Sciences Centre, University of Manchester, Central Manchester University Hospitals NHS Foundation Trust, Manchester M13 9WL, UK.
Alison CallawayWessex Regional Genetics Laboratory, Salisbury NHS Foundation Trust, Salisbury SP2 8BJ, UK.
Melissa CrenshawMedical Genetics, John Hopkins All Children's Hospital, St. Petersburg, FL 33701, USA.
Karin S CunhaDepartment of Pathology, School of Medicine, Universidade Federal Fluminense, Niterói 24220-900, Brazil.
Mitch CunninghamDivision of Genetic, Genomic and Metabolic Disorders, Children's Hospital of Michigan, Detroit Medical Center, Detroit, MI 48201, USA.
Maria D D'AgostinoDepartment of Medical Genetics, McGill University Health Centre, Montréal, QC H4A 3J1, Canada.
Karin DahanCenter for Human Genetics, Institute of Pathology and Genetics (IPG), Gosselies 6041, Belgium.
Alessandro De LucaMolecular Genetics Unit, Casa Sollievo della Sofferenza Hospital, IRCCS, San Giovanni Rotondo 71013, Italy.
Anne DestréeCenter for Human Genetics, Institute of Pathology and Genetics (IPG), Gosselies 6041, Belgium.
Radhika DhamijaDepartment of Clinical Genomics and Neurology, Mayo Clinic, Phoenix, AZ 85259, USA.
Marica EoliUnit of Molecular Neuro-Oncology, IRCCS Foundation, Carlo Besta Neurological Institute, Milan 20133, Italy.
D Gareth R EvansGenomic Medicine, Division of Evolution and Genomic Sciences, Manchester Academic Health Sciences Centre, University of Manchester, Central Manchester University Hospitals NHS Foundation Trust, Manchester M13 9WL, UK.
Patricia Galvin-PartonDepartment of Genetics, Stony Brook Children's, Stony Brook, NY 11794, USA.
Jaya K George-AbrahamDell Children's Medical Center of Central Texas, Austin, TX 78723, USA.
Karen W GrippDivision of Medical Genetics, Al DuPont Hospital for Children, Wilmington, DE 19803, USA.
Jose Guevara-CamposPediatrics Service, Felipe Guevara Rojas Hospital, University of Oriente, El Tigre-Anzoátegui, Venezuela 6034, Spain.
Neil A HanchardDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Concepcion Hernández-ChicoDepartment of Genetics, Hospital Universitario Ramón y Cayal, Institute of Health Research (IRYCIS), Madrid 28034, Spain and Center for Biomedical Research-Network of Rare Diseases (CIBERER).
LaDonna ImmkenDell Children's Medical Center of Central Texas, Austin, TX 78723, USA.
Sandra JanssensCenter for Medical Genetics, Ghent University Hospital, Ghent 9000, Belgium.
Kristi J JonesDepartment of Clinical Genetics, the Children's Hospital at Westmead, Westmead, NSW 2145, Australia.
Beth A KeenaDivision of Human Genetics, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Aaina KochharDepartment of Genetics, Valley Children's Healthcare, Madera, CA 93636, USA.
Jan LiebeltWomen's and Children's Hospital/SA Pathology, North Adelaide, SA 5006, Australia.
Arelis Martir-NegronDivision of Clinical Genetics, Center for Genomic Medicine, Miami Cancer Institute, Miami, FL 33176, USA.
Maurice J MahoneyDepartment of Genetics, Yale University, New Haven, CT 06520, USA.
Isabelle MaystadtCenter for Human Genetics, Institute of Pathology and Genetics (IPG), Gosselies 6041, Belgium.
Carey McDougallDivision of Human Genetics, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Meriel McEntagartSt George's University Hospitals NHS Foundation Trust, London SW17 0QT, UK.
Nancy MendelsohnGenomics Medicine Program, Children's Hospital Minnesota, Minneapolis, MN 55404, USA.
David T MillerMultidisciplinary Neurofibromatosis Program, Boston Children's Hospital, Boston, MA 02115, USA.
Geert MortierDepartment of Medical Genetics, University of Antwerp and Antwerp University Hospital, Antwerp 2650, Belgium.
Jenny MortonBirmingham Women's and Children's NHS Foundation Trust, Birmingham B15 2TG, UK.
John PappasDepartment of Pediatrics, Clinical Genetic Services, NYU School of Medicine, New York, NY 10016, USA.
Scott R PlotkinDepartment of Neurology and Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
Dinel PondGenomics Medicine Program, Children's Hospital Minnesota, Minneapolis, MN 55404, USA.
Kenneth RosenbaumDivision of Genetics and Metabolism, Children's National Health System, Washington, DC 20010, USA.
Karol RubinUniversity of Minnesota Health, Minneapolis, MN 55404, USA.
Laura RussellDepartment of Medical Genetics, McGill University Health Centre, Montréal, QC H4A 3J1, Canada.
Lane S RutledgeDepartment of Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Veronica SalettiDevelopmental Neurology Unit, IRCCS Foundation, Carlo Besta Neurological Institute, Milan 20133, Italy.
Rhonda SchonbergDivision of Genetics and Metabolism, Children's National Health System, Washington, DC 20010, USA.
Allison SchreiberGenomic Medicine Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
Meredith SeidelDepartment of Neurology and Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
Elizabeth SiqvelandGenomics Medicine Program, Children's Hospital Minnesota, Minneapolis, MN 55404, USA.
David W StocktonDivision of Genetic, Genomic and Metabolic Disorders, Children's Hospital of Michigan, Detroit Medical Center, Detroit, MI 48201, USA.
Eva TrevissonClinical Genetics Unit, Department of Women's and Children's Health, University of Padova, Padova, Italy and Italy Istituto di Ricerca Pediatria, IRP, Città della Speranza, Padova 35128, Italy.
Nicole J UllrichDepartment of Neurology, Boston Children's Hospital, Boston, MA 02115, USA.
Meena UpadhyayaDivision of Cancer and Genetics, Cardiff University, Cardiff CF14 4XN, UK.
Rick van MinkelenDepartment of Clinical Genetics, Erasmus Medical Center, Rotterdam 3015 GE, the Netherlands.
Helene VerhelstDepartment of Paediatrics, Division of Paediatric Neurology, Ghent University Hospital, Ghent 9000, Belgium.
Margaret R WallaceDepartment of Molecular Genetics & Microbiology, University of Florida College of Medicine, Gainesville, FL 32610, USA.
Yoon-Sim YapDivision of Medical Oncology, National Cancer Centre Singapore, Singapore 169610, Singapore; Faculty of Health Sciences, School of Medicine, University of Adelaide, Adelaide, SA 5000, Australia.
Elaine ZackaiDivision of Human Genetics, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Jonathan ZonanaDepartment of Molecular and Medical Genetics, Oregon Health and Science University, Portland, OR 97239, USA.
Vickie ZurcherGenomic Medicine Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
Kathleen ClaesCenter for Medical Genetics, Ghent University Hospital, Ghent 9000, Belgium.
Yolanda MartinDepartment of Genetics, Hospital Universitario Ramón y Cayal, Institute of Health Research (IRYCIS), Madrid 28034, Spain and Center for Biomedical Research-Network of Rare Diseases (CIBERER).
Bruce R KorfDepartment of Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Eric LegiusDepartment of Human Genetics, KU Leuven - University of Leuven, Leuven 3000, Belgium.
Ludwine M MessiaenDepartment of Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA. Electronic address: lmessiaen@uabmc.edu.
University of Alabama at Birmingham · USChildren’s Minnesota - St. Paul Hospital · USGhent University Hospital · BEInstitute of Pathology and Genetics · BEBoston Children's Hospital · USChildren's National · USCleveland Clinic · USDell Children's Medical Center of Central Texas · USFondazione IRCCS Istituto Neurologico Carlo Besta · ITMassachusetts General Hospital · USMcGill University Health Centre · CAPhiladelphia University · USSouth Australia Pathology · AUUniversity of Manchester · GBBaylor College of Medicine · USBirmingham Women’s and Children’s NHS Foundation Trust · GBCardiff University · GBCasa Sollievo della Sofferenza · ITCentre for Biomedical Network Research on Rare Diseases · ESChildren's Hospital at Westmead · AU
Funding
Mouse Neurodevelopmental Behavior CoreU54HD090255 · NICHD · BOSTON CHILDREN'S HOSPITAL · PI SAHIN, MUSTAFA · 2016 to 2020
$5.2MNICHD NIH HHS U54 HD090255
Abstract
Neurofibromatosis type 1 (NF1), a common genetic disorder with a birth incidence of 1:2,000-3,000, is characterized by a highly variable clinical presentation. To date, only two clinically relevant intragenic genotype-phenotype correlations have been reported for NF1 missense mutations affecting p.Arg1809 and a single amino acid deletion p.Met922del. Both variants predispose to a distinct mild NF1 phenotype with neither externally visible cutaneous/plexiform neurofibromas nor other tumors. Here, we report 162 individuals (129 unrelated probands and 33 affected relatives) heterozygous for a constitutional missense mutation affecting one of five neighboring NF1 codons-Leu844, Cys845, Ala846, Leu847, and Gly848-located in the cysteine-serine-rich domain (CSRD). Collectively, these recurrent missense mutations affect ∼0.8% of unrelated NF1 mutation-positive probands in the University of Alabama at Birmingham (UAB) cohort. Major superficial plexiform neurofibromas and symptomatic spinal neurofibromas were more prevalent in these individuals compared with classic NF1-affected cohorts (both p < 0.0001). Nearly half of the individuals had symptomatic or asymptomatic optic pathway gliomas and/or skeletal abnormalities. Additionally, variants in this region seem to confer a high predisposition to develop malignancies compared with the general NF1-affected population (p = 0.0061). Our results demonstrate that these NF1 missense mutations, although located outside the GAP-related domain, may be an important risk factor for a severe presentation. A genotype-phenotype correlation at the NF1 region 844-848 exists and will be valuable in the management and genetic counseling of a significant number of individuals.
Indexed as
Genetic Association StudiesAdolescentAmino Acid SequenceChildCodonCohort StudiesComputer SimulationDemographyFemaleHeterozygoteHumansMaleMutation, MissenseNeurofibromatosis 1Neurofibromin 1PhenotypeCodonNeurofibromin 1codons 844–848CSRDgenotype-phenotype correlationmissense mutationMPNSTneurofibromatosis type 1NF1plexiform neurofibromaspinal NF
Identifiers
What OpenQuestion holds
Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390
Registered trials
None linked
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.