Evidence map›Paper›PMID 31949314›Full record

ArticleGenetics in medicine : official journal of the American College of Medical Genetics2020

GATAD2B-associated neurodevelopmental disorder (GAND): clinical and molecular insights into a NuRD-related disorder.

Christine Shieh, Natasha Jones, Brigitte Vanle, Margaret Au, Alden Y Huang, Ana P G Silva, Hane Lee, Emilie D Douine, Maria G Otero, Andrew Choi and 46 more

Erratum issued Registry-linked trialOpen access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT02450851 (Clinical and Genetic Evaluation of Patients With Undiagnosed Disorders Through the Undiagnosed Diseases Network), which is not on this map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
5.0field-weighted citation impact, top 5% of its field
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.

NCT02450851 recruitingnot on this map

Clinical and Genetic Evaluation of Patients With Undiagnosed Disorders Through the Undiagnosed Diseases Network

TypeobservationalSponsorNational Human Genome Research Institute (NHGRI)Ran2015 to 2028Enrolled20,000ConditionsGenetic Disease
3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 33 citations in OpenAlex.

  1. Role of CHD chromatin remodelers in heart development.World journal of pediatrics : WJP · 2026
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  8. Parental gonadossomatic mosaicism inFrontiers in genetics · 2023
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  10. Integrated gene analyses of de novo variants from 46,612 trios with autism and developmental disorders.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  11. Sca1Stem cell reviews and reports · 2021
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  14. Chromatin Remodeling in the Brain-aInternational journal of molecular sciences · 2021
    Review
  15. Article
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  17. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

56 authors at 20 institutions in 6 countries.

Christine ShiehDavid Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Natasha JonesSchool of Life and Environmental Sciences, University of Sydney, Sydney, NSW, Australia.
Brigitte VanleDepartment of Psychiatry & Behavioral Neurosciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Margaret AuDepartment of Pediatrics Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Alden Y HuangInstitute for Precision Health, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA.
Ana P G SilvaSchool of Life and Environmental Sciences, University of Sydney, Sydney, NSW, Australia.
Hane LeeDepartment of Human Genetics and Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA.
Emilie D DouineDepartment of Human Genetics, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA.
Maria G OteroBoard of Governor's Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Andrew ChoiBoard of Governor's Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Katheryn GrandDepartment of Pediatrics, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Ingrid P TaffDepartment of Neurology, Hofstra School of Medicine, Great Neck, NY, USA.
Mauricio R DelgadoDepartment of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center and Texas Scottish Rite Hospital for Children, Dallas, TX, USA.
M J HajianpourDepartment of Pediatrics, Division of Medical Genetics, East Tennessee State University, Quillen College of Medicine, Mountain Home, TN, USA.
Andrea SeeleyGeisinger Medical Center, Danville, PA, USA.
Luis RohenaDivision of Genetics, Department of Pediatrics, Brooke Army Medical Center, Fort Sam Houston, TX, USA.
Hilary VernonMcKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Balitmore, MD, USA.
Karen W GrippDivision of Medical Genetics, Al DuPont Hospital for Children, Wilmington, DE, USA.
Samantha A VerganoDivision of Medical Genetics and Metabolism, Children's Hospital of The King's Daughters, Norfolk, VA, USA.
Sonal MahidaDepartment of Neurogenetics, Kennedy Krieger Institute, Baltimore, MD, USA.
Sakkubai NaiduDepartment of Neurology and Pediatrics, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Ana Berta SousaServiço de Genética Médica, Hospital Santa Maria, CHULN, Lisboa, Portugal and Faculdade de Medicina de Lisboa, Universidade de Lisboa, Lisboa, Portugal.
Karen E WainAutism & Developmental Medicine Institute, Geisinger, Lewisburg, PA, USA.
Thomas D ChallmanAutism & Developmental Medicine Institute, Geisinger, Lewisburg, PA, USA.
Geoffrey BeekChildren's Hospitals and Clinics of Minnesota Department of Genetics, Minneapolis, MN, USA.
Donald BaselDepartment of Pediatrics, Division of Genetics; Children's Hospital of Wisconsin, Milwaukee, WI, USA.
Judith RanellsDivision of Genetics and Metabolism, Department of Pediatrics, University of South Florida, Tampa, FL, USA.
Rosemarie SmithDepartment of Pediatrics, Division of Genetics, Maine Medical Center, Portland, ME, USA.
Roman YusupovDivision of Clinical Genetics, Joe DiMaggio Children's Hospital, Hollywood, FlL, USA.
Mary-Louise FreckmannRoyal North Shore Hospital, St Leonards, NSW, Australia.
Lisa OhdenDepartment of Genetic Counseling, Sanford Children's Specialty Clinic, Sioux Falls, SD, USA.
Laura Davis-KeppenDepartment of Pediatrics, Sanford School of Medicine of the University of South Dakota, Sioux Falls, SD, USA.
David ChitayatThe Prenatal Diagnosis and Medical Genetics Program, Department of Obstetrics and Gynecology, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada.
James J DowlingDivision of Neurology, Department of Pediatrics, The Hospital for Sick Children, Toronto, ON, Canada.
Richard FinkelDivision of Pediatric Neurology, Department of Pediatrics, Nemours Children's Hospital, Orlando, FL, USA.
Andrew DauberDivision of Endocrinology, Children's National Health System, Washington, DC, USA.
Rebecca SpillmannDepartment of Pediatrics, Division of Medical Genetics, Duke University Medical Center, Durham, NC, USA.
Loren D M PenaDivision of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Undiagnosed Diseases Network
Kay MetcalfeManchester Centre for Genomic Medicine, Manchester University NHS FT, Manchester, UK.
Miranda SplittInstitute of Genetic Medicine, Northern Genetics Service, Newcastle upon Tyne Hospitals Trust, Newcastle, UK.
Katherine LachlanFaculty of Medicine, University of Southampton, Southampton, UK.
Shane A McKeeNorthern Ireland Regional Genetics Service, Belfast City Hospital, Belfast, UK.
Jane HurstDepartment of Clinical Genetics, NE Thames Genetics Service, Great Ormond Street Hospital, London, UK.
David R FitzpatrickMedical Research Council Human Genetics Unit, University of Edinburgh, Edinburgh, UK.
Jenny E V MortonWest Midlands Regional Clinical Genetics Service and Birmingham Health Partners, Birmingham, UK.
Helen CoxWest Midlands Regional Clinical Genetics Service and Birmingham Health Partners, Birmingham, UK.
Sunita VenkateswaranDivision of Neurology, Department of Pediatrics, Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, ON, Canada.
Juan I YoungJohn P Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA.
Eric D MarshDivision of Neurology, Children's Hospital of Philadelphia and Department of Neurology and Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Stanley F NelsonDepartment of Human Genetics, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA.
Julian A MartinezDepartment of Human Genetics; Division of Medical Genetics, Department of Pediatrics; David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
John M GrahamDepartment of Pediatrics, Medical Genetics, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Usha KiniOxford Centre for Genomic Medicine, Oxford University Hospital NHS Foundation Trust, Oxford, UK.
Joel P MackaySchool of Life and Environmental Sciences, University of Sydney, Sydney, NSW, Australia.
Tyler Mark PiersonDepartment of Pediatrics, Cedars-Sinai Medical Center, Los Angeles, CA, USA. Tyler.Pierson@cshs.org.ORCID http://orcid.org/0000-0003-1985-3671
Cedars-Sinai Medical Center · USUniversity of California, Los Angeles · USThe University of Sydney · AUAutism & Developmental Medicine Institute · USBirmingham Women's Hospital · GBKennedy Krieger Institute · USBrooke Army Medical Center · USChildren's Hospital of Philadelphia · USChildren's Hospital of The King's Daughters · USChildren's Hospital of Wisconsin · USChildren's Minnesota · USChildren's National · USCincinnati Children's Hospital Medical Center · USDuke Medical Center · USDuPont (United States) · USEast Tennessee State University · USGeisinger Medical Center · USGreat Ormond Street Hospital · GBHofstra University · USHospital for Sick Children · CA

Funding

UCLA Clinical Translational Science InstituteUL1TR001881 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARLEEN F. BROWN, ARASH NAEIM · 2016 to 2026
$118.1M
An integrated and diverse genomic medicine program for undiagnosed diseasesU01HG007672 · NHGRI · DUKE UNIVERSITY · PI SHASHI, VANDANA · 2014 to 2022
$13.4M
The Intellectual and Developmental Disabilities Research Center at CHOP/PennU54HD086984 · NICHD · CHILDREN'S HOSP OF PHILADELPHIA · PI SCHULTZ, ROBERT THOMAS · 2016 to 2020
$6.3M
Medical Research Council MC_PC_16018Medical Research Council MC_UU_00007/3NCATS NIH HHS UL1 TR001881NHGRI NIH HHS U01 HG007672NICHD NIH HHS U54 HD086984
6 · The paper itself

Abstract

purposeDetermination of genotypic/phenotypic features of GATAD2B-associated neurodevelopmental disorder (GAND).

methodsFifty GAND subjects were evaluated to determine consistent genotypic/phenotypic features. Immunoprecipitation assays utilizing in vitro transcription-translation products were used to evaluate GATAD2B missense variants' ability to interact with binding partners within the nucleosome remodeling and deacetylase (NuRD) complex.

resultsSubjects had clinical findings that included macrocephaly, hypotonia, intellectual disability, neonatal feeding issues, polyhydramnios, apraxia of speech, epilepsy, and bicuspid aortic valves. Forty-one novelGATAD2B variants were identified with multiple variant types (nonsense, truncating frameshift, splice-site variants, deletions, and missense). Seven subjects were identified with missense variants that localized within two conserved region domains (CR1 or CR2) of the GATAD2B protein. Immunoprecipitation assays revealed several of these missense variants disrupted GATAD2B interactions with its NuRD complex binding partners.

conclusionsA consistent GAND phenotype was caused by a range of genetic variants in GATAD2B that include loss-of-function and missense subtypes. Missense variants were present in conserved region domains that disrupted assembly of NuRD complex proteins. GAND's clinical phenotype had substantial clinical overlap with other disorders associated with the NuRD complex that involve CHD3 and CHD4, with clinical features of hypotonia, intellectual disability, cardiac defects, childhood apraxia of speech, and macrocephaly.

Indexed as

Intellectual DisabilityMegalencephalyNeurodevelopmental DisordersChildFemaleGATA Transcription FactorsHumansNucleosomesPhenotypePregnancyRepressor ProteinsGATAD2B protein, humanGATA Transcription FactorsNucleosomesRepressor ProteinsGATAD2B; NuRD complex; apraxia of speech; chromatin remodeling; macrocephaly

Identifiers

PMID31949314
PMCPMC7920571
OpenAlexW3000679810

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Registered trials

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.