ArticleHuman mutation2020
Clinical spectrum of individuals with pathogenic NF1 missense variants affecting p.Met1149, p.Arg1276, and p.Lys1423: genotype-phenotype study in neurofibromatosis type 1.
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Article in Human mutation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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Who cites it
76 citing papers in PubMed.
- Relation Between Genotype and Behavioral Phenotype in Children and Adolescents With Neurofibromatosis Type 1.JAACAP open · 2026Article
- Article
- Diagnoses of double heterozygous NF1 variants and dual RASopathy.Molecular and cellular pediatrics · 2026Review
- Pathogenic Neurofibromatosis type 1 gene variants in tumors of non-NF1 patients and role of R1276.FEBS open bio · 2026Article
- Aorto-Renal Dysplasia in Childhood: The Overlap of Neurofibromatosis Type 1 and Pediatric Renovascular Hypertension.Current hypertension reports · 2026Review
- Neurovascular Issues in Neurofibromatosis Type I: Focus on Intracranial Stenosis.Life (Basel, Switzerland) · 2026Review
- Bilateral pheochromocytoma as a late presentation of neurofibromatosis type 1.Endocrinology, diabetes & metabolism case reports · 2026Article
- Colon cancer in a patient with a mosaic monoallelic germline pathogenicExploration of neuroscience · 2026Article
- Whole-genome sequencing in Brazilian patients with neurofibromatosis type 1, including novel variants, incidental findings, and dual diagnoses.Einstein (Sao Paulo, Brazil) · 2026Article
- Synonymous and non-synonymous variants at splice junctions can disrupt splicing and are frequently linked to disease associated loss of function genes.BMC genomics · 2025Article
- Protein domain-specific genotype-phenotype correlation study of neurofibromatosis type 1.Scientific reports · 2025Article
- The spectrum of pathogenic NF1 variants in participants enrolling on clinical trials of MEK inhibitors for plexiform neurofibroma.Human genetics · 2025Article
- Subtype distribution, clinical presentation, and molecular spectrum of neurofibromatosis type 1-associated breast cancer.Breast (Edinburgh, Scotland) · 2025Article
- Unveiling the complexity of neurofibromatosis type 1: Innovations in genetic understanding and clinical management. A narrative review.Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia · 2025Review
- Refined genotype-phenotype correlations in neurofibromatosis type 1 patients withJournal of medical genetics · 2025Article
- Article
- 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
- Genetic analysis of 25 Chinese pedigrees with neurofibromatosis type 1 and genotype-phenotype study from an extended cohort.Orphanet journal of rare diseases · 2025Article
- Review
- Neurofibromatosis-Noonan syndrome: a prospective monocentric study of 26 patients and literature review.Orphanet journal of rare diseases · 2025Review
16 more citing papers are in PubMed but not listed here.
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Authors and funding
108 authors.
Magdalena KoczkowskaDepartment of Genetics, University of Alabama at Birmingham, Birmingham, Albama.
Tom CallensDepartment of Genetics, University of Alabama at Birmingham, Birmingham, Albama.
Yunjia ChenDepartment of Genetics, University of Alabama at Birmingham, Birmingham, Albama.
Alicia GomesDepartment of Genetics, University of Alabama at Birmingham, Birmingham, Albama.
Alesha D HicksDepartment of Genetics, University of Alabama at Birmingham, Birmingham, Albama.
Angela SharpDepartment of Genetics, University of Alabama at Birmingham, Birmingham, Albama.
Eric JohnsDepartment of Genetics, University of Alabama at Birmingham, Birmingham, Albama.
Kim Armfield UhasChildren's Healthcare of Atlanta at Scottish Rite, Atlanta, Georgia.
Linlea ArmstrongDepartment of Medical Genetics, BC Women's Hospital, University of British Columbia, Vancouver, British Columbia, Canada.
Katherine Armstrong BosankoDivision of Clinical Genetics and Metabolism, Arkansas Children's Hospital, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
Dusica Babovic-VuksanovicDepartment of Clinical Genomics, Mayo Clinic, Rochester, Minnesota.
Laura BakerDivision of Medical Genetics, Al DuPont Hospital for Children, Wilmington, Delaware.
Donald G BaselChildren's Hospital of Wisconsin, Milwaukee, Wisconsin.
Mario BengalaU.O.C Laboratorio di Genetica Medica, Dipartimento di Oncoematologia, Fondazione Policlinico di Tor Vergata, Rome, Italy.
James T BennettDivision of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, Washington.
Chelsea ChambersDepartment of Neurology, University of Virginia Medical Center, Charlottesville, Virginia.
Lola K ClarksonGreenwood Genetic Center, Greenwood, South Carolina.
Maurizio ClementiClinical Genetics Unit, Department of Women's and Children's Health, University of Padova, Padova, Italy.
Fanny M CortésCenter for Rare Diseases, Clinica Las Condes, Santiago, Chile.
Mitch CunninghamDivision of Genetic, Genomic, and Metabolic Disorders, Detroit Medical Center, Children's Hospital of Michigan, Detroit, Michigan.
M Daniela D'AgostinoDivision of Medical Genetics, McGill University Health Centre, Montréal, Quebec, Canada.
Martin B DelatyckiBruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute, Parkville, Victoria, Australia.
Maria C DigilioMedical Genetics Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Laura DosaSOC Genetica Medica, AOU Meyer, Florence, Italy.
Silvia EspositoDevelopmental Neurology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
Stephanie FoxDivision of Medical Genetics, McGill University Health Centre, Montréal, Quebec, Canada.
Mary-Louise FreckmannDepartment of Clinical Genetics, Royal North Shore Hospital, St Leonards, New South Wales, Australia.
Christine FauthDivision of Human Genetics, Medical University of Innsbruck, Innsbruck, Austria.
Teresa GiuglianoDepartment of Precision Medicine, Università degli Studi della Campania "Luigi Vanvitelli", Naples, Italy.
Sandra GiustiniDepartment of Dermatology and Venereology, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy.
Allison GoetschDepartment of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
Yael GoldbergThe Raphael Recanati Genetics Institute, Rabin Medical Center, Petah Tikva, Israel.
Robert S GreenwoodDivision of Child Neurology, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
Cristin GriffisChildren's Hospital of Wisconsin, Milwaukee, Wisconsin.
Karen W GrippDivision of Medical Genetics, Al DuPont Hospital for Children, Wilmington, Delaware.
Punita GuptaNeurofibromatosis Diagnostic and Treatment Program, St. Joseph's Children's Hospital, Paterson, New Jersey.
Eric HaanAdult Genetics Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia.
Rachel K HachenNeurofibromatosis Program, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Tamara L HaygarthCarolinas HealthCare System, Levine Children's Specialty Center, Charlotte, North Carolina.
Concepción Hernández-ChicoDepartment of Genetics, Hospital Universitario Ramón y Cajal, Institute of Health Research (IRYCIS) and Center for Biomedical Research-Network of Rare Diseases (CIBERER), Madrid, Spain.
Katelyn HodgeDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana.
Robert J HopkinDivision of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Louanne HudginsDivision of Medical Genetics, Stanford University School of Medicine, Stanford, California.
Sandra JanssensCenter for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
Kory KellerDepartment of Molecular and Medical Genetics, Oregon Health and Science University, Portland, Oregon.
Geraldine Kelly-MancusoDivision of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Aaina KochharDepartment of Medical Genetics and Metabolism, Valley Children's Healthcare, Madera, California.
Bruce R KorfDepartment of Genetics, University of Alabama at Birmingham, Birmingham, Albama.
Andrea M LewisDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.
Jan LiebeltThe South Australian Clinical Genetics Service at the Women's and Children's Hospital, North Adelaide, South Australia, Australia.
Angie LichtyGreenwood Genetic Center, Greenwood, South Carolina.
Robert H ListernickDepartment of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
Michael J LyonsGreenwood Genetic Center, Greenwood, South Carolina.
Isabelle MaystadtCenter for Human Genetics, Institute of Pathology and Genetics (IPG), Gosselies, Belgium.
Mayra Martinez OjedaDivision of Genetics and Genomics, Boston Children's Hospital, Boston, Massachusetts.
Carey McDougallDivision of Human Genetics, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.
Lesley K McGregorThe South Australian Clinical Genetics Service at the Women's and Children's Hospital, North Adelaide, South Australia, Australia.
Daniela MelisSection of Pediatrics, Department of Translational Medical Sciences, Federico II University, Naples, Italy.
Nancy MendelsohnGenomics Medicine Program, Children's Hospital Minnesota, Minneapolis, Minnesota.
Malgorzata J M NowaczykDepartment of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
June OrtenbergDivision of Medical Genetics, McGill University Health Centre, Montréal, Quebec, Canada.
Karin PanzerUniversity of Iowa Stead Family Children's Hospital, Iowa City, Iowa.
John G PappasDivision of Clinical Genetic Services, Department of Pediatrics, NYU School of Medicine, New York, New York.
Mary Ella PierpontDepartment of Pediatrics and Opthalmology, University of Minnesota, Minneapolis, Minnesota.
Giulio PilusoDepartment of Precision Medicine, Università degli Studi della Campania "Luigi Vanvitelli", Naples, Italy.
Valentina PinnaMolecular Genetics Unit, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy.
Eniko K PivnickDepartment of Pediatrics and Department of Ophthalmology, University of Tennessee Health Science Center, Memphis, Tennessee.
Dinel A PondGenomics Medicine Program, Children's Hospital Minnesota, Minneapolis, Minnesota.
Cynthia M PowellDepartment of Genetics and Department of Pediatrics, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
Caleb RogersDepartment of Molecular and Medical Genetics, Oregon Health and Science University, Portland, Oregon.
Noa Ruhrman ShaharThe Raphael Recanati Genetics Institute, Rabin Medical Center, Petah Tikva, Israel.
S Lane RutledgeDepartment of Genetics, University of Alabama at Birmingham, Birmingham, Albama.
Veronica SalettiDevelopmental Neurology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
Sarah A SandaraduraDivision of Clinical Genetics, Department of Paediatrics and Child Health, Children's Hospital at Westmead, University of Sydney, Sydney, New South Wales, Australia.
Claudia SantoroSpecialistic and General Surgery Unit, Department of Woman and Child, Referral Centre of Neurofibromatosis, Università degli Studi della Campania "Luigi Vanvitelli", Naples, Italy.
Ulrich A SchatzDivision of Human Genetics, Medical University of Innsbruck, Innsbruck, Austria.
Allison SchreiberCleveland Clinic, Genomic Medicine Institute, Cleveland, Ohio.
Daryl A ScottDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.
Elizabeth A SellarsDivision of Clinical Genetics and Metabolism, Arkansas Children's Hospital, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
Ruth ShefferDepartment of Genetics and Metabolic Diseases, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Elizabeth SiqvelandGenomics Medicine Program, Children's Hospital Minnesota, Minneapolis, Minnesota.
John M SlopisDepartment of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Rosemarie SmithDivision of Genetics, Department of Pediatrics, Maine Medical Center, Portland, Maine.
Alberto SpaliceChild Neurology Division, Department of Pediatrics, Sapienza University of Rome, Rome, Italy.
David W StocktonDivision of Genetic, Genomic, and Metabolic Disorders, Detroit Medical Center, Children's Hospital of Michigan, Detroit, Michigan.
Haley StreffDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.
Amy TheosDepartment of Dermatology, University of Alabama at Birmingham, Birmingham, Alabama.
Gail E TomlinsonDivision of Pediatric Hematology-Oncology, Greehey Children's Cancer Research Institute, The University of Texas Health Science Center, San Antonio, Texas.
Grace TranDepartment of Clinical Cancer Genetics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Pamela L TrapaneDivision of Pediatric Genetics, Department of Pediatrics, University of Florida College of Medicine, Jacksonville, Florida.
Eva TrevissonClinical Genetics Unit, Department of Women's and Children's Health, University of Padova, Padova, Italy.ORCID 0000-0002-5380-6265
Nicole J UllrichDepartment of Neurology, Boston Children's Hospital, Boston, Massachusetts.
Jenneke Van den EndeCenter for Medical Genetics, University of Antwerp and Antwerp University Hospital, Antwerp, Belgium.
Samantha A Schrier VerganoDivision of Medical Genetics and Metabolism, Children's Hospital of the King's Daughters, Norfolk, Virginia.
Stephanie E WallaceDivision of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, Washington.
Michael F WanglerDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.ORCID 0000-0001-5245-5910
David D WeaverDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana.
Kaleb H YohayDepartment of Neurology, New York University School of Medicine, Langone Medical Center, New York, New York.
Elaine ZackaiDivision of Human Genetics, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.
Jonathan ZonanaDepartment of Molecular and Medical Genetics, Oregon Health and Science University, Portland, Oregon.
Vickie ZurcherCleveland Clinic, Genomic Medicine Institute, Cleveland, Ohio.
Kathleen B M ClaesCenter for Medical Genetics, Ghent University Hospital, Ghent, Belgium.ORCID 0000-0003-0841-7372
Marica EoliDivision of Molecular Neuro-Oncology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
Yolanda MartinDepartment of Genetics, Hospital Universitario Ramón y Cajal, Institute of Health Research (IRYCIS) and Center for Biomedical Research-Network of Rare Diseases (CIBERER), Madrid, Spain.
Katharina WimmerDivision of Human Genetics, Medical University of Innsbruck, Innsbruck, Austria.ORCID 0000-0002-0732-7538
Alessandro De LucaMolecular Genetics Unit, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy.ORCID 0000-0002-4408-8062
Eric LegiusDepartment of Human Genetics, KU Leuven, Leuven, Belgium.
Ludwine M MessiaenDepartment of Genetics, University of Alabama at Birmingham, Birmingham, Albama.ORCID 0000-0002-1136-0154
Funding
Mouse Neurodevelopmental Behavior CoreU54HD090255 · NICHD · BOSTON CHILDREN'S HOSPITAL · PI SAHIN, MUSTAFA · 2016 to 2020
$5.2MNICHD NIH HHS U54 HD090255
Abstract
We report 281 individuals carrying a pathogenic recurrent NF1 missense variant at p.Met1149, p.Arg1276, or p.Lys1423, representing three nontruncating NF1 hotspots in the University of Alabama at Birmingham (UAB) cohort, together identified in 1.8% of unrelated NF1 individuals. About 25% (95% confidence interval: 20.5-31.2%) of individuals heterozygous for a pathogenic NF1 p.Met1149, p.Arg1276, or p.Lys1423 missense variant had a Noonan-like phenotype, which is significantly more compared with the "classic" NF1-affected cohorts (all p < .0001). Furthermore, p.Arg1276 and p.Lys1423 pathogenic missense variants were associated with a high prevalence of cardiovascular abnormalities, including pulmonic stenosis (all p < .0001), while p.Arg1276 variants had a high prevalence of symptomatic spinal neurofibromas (p < .0001) compared with "classic" NF1-affected cohorts. However, p.Met1149-positive individuals had a mild phenotype, characterized mainly by pigmentary manifestations without externally visible plexiform neurofibromas, symptomatic spinal neurofibromas or symptomatic optic pathway gliomas. As up to 0.4% of unrelated individuals in the UAB cohort carries a p.Met1149 missense variant, this finding will contribute to more accurate stratification of a significant number of NF1 individuals. Although clinically relevant genotype-phenotype correlations are rare in NF1, each affecting only a small percentage of individuals, together they impact counseling and management of a significant number of the NF1 population.
Indexed as
AllelesGenetic Association StudiesGenetic Predisposition to DiseaseMutation, MissenseAmino Acid SubstitutionCross-Sectional StudiesHeterozygoteHumansNeurofibromatosis 1Neurofibromin 1PhenotypeNeurofibromin 1genotype-phenotype correlationNF1p.Arg1276p.Lys1423p.Met1149
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