Evidence map›Paper›PMID 30190611›Full record

ArticleGenetics in medicine : official journal of the American College of Medical Genetics2019

Expanding the clinical phenotype of individuals with a 3-bp in-frame deletion of the NF1 gene (c.2970_2972del): an update of genotype-phenotype correlation.

Magdalena Koczkowska, Tom Callens, Alicia Gomes, Angela Sharp, Yunjia Chen, Alesha D Hicks, Arthur S Aylsworth, Amedeo A Azizi, Donald G Basel, Gary Bellus and 60 more

Erratum issuedAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 62 papers.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

62 citing papers in PubMed.

  1. Trial
  2. Observational
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Cells · 2024
    Review
  19. Article
  20. Article

2 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

70 authors.

Magdalena KoczkowskaDepartment of Genetics, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Tom CallensDepartment of Genetics, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Alicia GomesDepartment of Genetics, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Angela SharpDepartment of Genetics, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Yunjia ChenDepartment of Genetics, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Alesha D HicksDepartment of Genetics, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Arthur S AylsworthDepartments of Pediatrics and Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Amedeo A AziziDivision of Neonatology, Pediatric Intensive Care and Neuropediatrics, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria.
Donald G BaselChildren's Hospital of Wisconsin, Milwaukee, Wisconsin, USA.
Gary BellusDepartment of Clinical Genetics and Metabolism, Children's Hospital, University of Colorado School of Medicine, Aurora, Colorado, USA.
Lynne M BirdDepartment of Pediatrics, University of California San Diego; Division of Genetics/Dysmorphology, Rady Children's Hospital, San Diego, California, USA.
Maria A BlazoBaylor Scott and White Hospital, Temple, Texas, USA.
Leah W BurkeClinical Genetics Program, University of Vermont Medical Center, Burlington, Vermont, USA.
Ashley CannonDepartment of Genetics, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Felicity CollinsDepartment of Clinical Genetics, The Children's Hospital at Westmead, Westmead, New South Wales, Australia.
Colette DeFilippoDepartment of Pediatrics, Division of Genomic Medicine, UC Davis MIND Institute, Sacramento, California, USA.
Ellen DenayerDepartment of Human Genetics, KU Leuven-University of Leuven, Leuven, Belgium.
Maria C DigilioMedical Genetics Unit, Bambino Gesù Children's, IRCCS, Rome, Italy.
Shelley K DillsCarolinas Medical Center, Charlotte, North Carolina, USA.
Laura DosaSOC Genetica Medica, AOU Meyer, Florence, Italy.
Robert S GreenwoodDepartment of Neurology, Division of Child Neurology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.
Cristin GriffisChildren's Hospital of Wisconsin, Milwaukee, Wisconsin, USA.
Punita GuptaNeurofibromatosis Diagnostic & Treatment Program, St. Joseph's Children's Hospital, Paterson, New Jersey, USA.
Rachel K HachenNeurofibromatosis Program, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Concepción Hernández-ChicoDepartment of Genetics, Hospital Universitario Ramón y Cajal, Institute of Health Research (IRYCIS), Madrid, Spain.
Sandra JanssensCenter for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
Kristi J JonesDepartment of Clinical Genetics, The Children's Hospital at Westmead, Westmead, New South Wales, Australia.
Justin T JordanDepartment of Neurology and Cancer Center, Massachusetts General Hospital, Boston, Massachusetts, USA.
Peter KannuDivision of Clinical and Metabolic Genetics, The Hospital for Sick Children, Toronto, Ontario, Canada.
Bruce R KorfDepartment of Genetics, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Andrea M LewisDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
Robert H ListernickDepartment of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Fortunato LonardoMedical Genetics Unit, G. Rummo Hospital, Benevento, Italy.
Maurice J MahoneyDepartment of Genetics, Yale University, New Haven, Connecticut, USA.
Mayra Martinez OjedaDivision of Genetics and Genomics, Boston Children's Hospital, Boston, Massachusetts, USA.
Marie T McDonaldDepartment of Pediatrics, Division of Medical Genetics, Duke University School of Medicine, Durham, North Carolina, USA.
Carey McDougallDivision of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Nancy MendelsohnGenomics Medicine Program, Children's Hospital Minnesota, Minneapolis, Minnesota, USA.
David T MillerDivision of Genetics and Genomics, Boston Children's Hospital, Boston, Massachusetts, USA.
Mari MoriDepartment of Pediatrics, Warren Alpert Medical School, Brown University, Providence, Rhode Island, USA.
Rianne OostenbrinkDepartment of General Pediatrics, Erasmus MC-Sophia, Rotterdam, The Netherlands.
Sebastién PerreaultCHU Sainte-Justine, Mother and Child University Hospital Center, Montréal, Québec, Canada.
Mary Ella PierpontDepartment of Pediatrics and Ophthalmology, University of Minnesota, Minneapolis, Minnesota, USA.
Carmelo PiscopoU.O.S.C. Medical Genetics, A.O.R.N. "A. Cardarelli", Naples, Italy.
Dinel A PondGenomics Medicine Program, Children's Hospital Minnesota, Minneapolis, Minnesota, USA.
Linda M RandolphDivision of Medical Genetics, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Katherine A RauenDepartment of Pediatrics, Division of Genomic Medicine, UC Davis MIND Institute, Sacramento, California, USA.
Surya RednamDepartment of Pediatrics, Section of Hematology-Oncology, Baylor College of Medicine, Houston, Texas, USA.
S Lane RutledgeDepartment of Genetics, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Veronica SalettiDevelopmental Neurology Unit, IRCCS Foundation, Carlo Besta Neurological Institute, Milan, Italy.
G Bradley SchaeferDivision of Medical Genetics, University of Arkansas for Medical Sciences, Arkansas Children's Hospital, Little Rock, Arkansas, USA.
Elizabeth K SchorryDivision of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Daryl A ScottDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
Andrea ShugarDivision of Clinical and Metabolic Genetics, The Hospital for Sick Children, Toronto, Ontario, Canada.
Elizabeth SiqvelandGenomics Medicine Program, Children's Hospital Minnesota, Minneapolis, Minnesota, USA.
Lois J StarrGenetic Medicine, Munroe-Meyer Institute, University of Nebraska Medical Center, Omaha, Nebraska, USA.
Ashraf SyedDCH Regional Medical Center and Northport Medical Center, Northport, Alabama, USA.
Pamela L TrapaneStead Family Department of Pediatrics, University of Iowa Hospitals & Clinics, Iowa City, Iowa, USA.
Nicole J UllrichDepartment of Neurology, Boston Children's Hospital, Boston, Massachusetts, USA.
Emily G WakefieldDivision of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Laurence E WalshDepartment of Neurology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Michael F WanglerDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
Elaine ZackaiDivision of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Kathleen B M ClaesCenter for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
Katharina WimmerDivision of Human Genetics, Medical University of Innsbruck, Innsbruck, Austria.
Rick van MinkelenDepartment of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands.
Alessandro De LucaIRCCS Casa Sollievo della Sofferenza, Molecular Genetics Unit, San Giovanni Rotondo, Foggia, Italy.
Yolanda MartinDepartment of Genetics, Hospital Universitario Ramón y Cajal, Institute of Health Research (IRYCIS), Madrid, Spain.
Eric LegiusDepartment of Human Genetics, KU Leuven-University of Leuven, Leuven, Belgium.
Ludwine M MessiaenDepartment of Genetics, University of Alabama at Birmingham, Birmingham, Alabama, USA. lmessiaen@uabmc.edu.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeNeurofibromatosis type 1 (NF1) is characterized by a highly variable clinical presentation, but almost all NF1-affected adults present with cutaneous and/or subcutaneous neurofibromas. Exceptions are individuals heterozygous for the NF1 in-frame deletion, c.2970_2972del (p.Met992del), associated with a mild phenotype without any externally visible tumors.

methodsA total of 135 individuals from 103 unrelated families, all carrying the constitutional NF1 p.Met992del pathogenic variant and clinically assessed using the same standardized phenotypic checklist form, were included in this study.

resultsNone of the individuals had externally visible plexiform or histopathologically confirmed cutaneous or subcutaneous neurofibromas. We did not identify any complications, such as symptomatic optic pathway gliomas (OPGs) or symptomatic spinal neurofibromas; however, 4.8% of individuals had nonoptic brain tumors, mostly low-grade and asymptomatic, and 38.8% had cognitive impairment/learning disabilities. In an individual with the NF1 constitutional c.2970_2972del and three astrocytomas, we provided proof that all were NF1-associated tumors given loss of heterozygosity at three intragenic NF1 microsatellite markers and c.2970_2972del.

conclusionWe demonstrate that individuals with the NF1 p.Met992del pathogenic variant have a mild NF1 phenotype lacking clinically suspected plexiform, cutaneous, or subcutaneous neurofibromas. However, learning difficulties are clearly part of the phenotypic presentation in these individuals and will require specialized care.

Indexed as

AdolescentAdultChildChild, PreschoolFemaleGenetic Association StudiesGenetic Predisposition to DiseaseHeterozygoteHumansInfantLearning DisabilitiesMaleMutation, MissenseNeurofibroma, PlexiformNeurofibromatosis 1Neurofibromin 1Neurofibromin 1genotype–phenotype correlationlearning difficultiesneurofibromaNF1p.Met992del

Identifiers

PMID30190611
PMCPMC6752285

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.