Evidence map›Paper›PMID 32693025›Full record

ArticleAmerican journal of human genetics2020

De Novo Variants in the ATPase Module of MORC2 Cause a Neurodevelopmental Disorder with Growth Retardation and Variable Craniofacial Dysmorphism.

Maria J Guillen Sacoto, Iva A Tchasovnikarova, Erin Torti, Cara Forster, E Hallie Andrew, Irina Anselm, Kristin W Baranano, Lauren C Briere, Julie S Cohen, William J Craigen and 38 more

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

Article in American journal of human genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. 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 62 papers.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed
5.3field-weighted citation impact, top 3% 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

62 citing papers in PubMed, 108 citations in OpenAlex.

  1. Review
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  19. Review
  20. A Novel HeterozygousCase reports in genetics · 2024
    Article

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

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

48 authors at 20 institutions in 3 countries.

Maria J Guillen SacotoGeneDx, Inc., Gaithersburg, MD 20877, USA. Electronic address: mguillen@genedx.com.
Iva A TchasovnikarovaDepartment of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Genetics, Harvard Medical School, Boston, MA 02114, USA.
Erin TortiGeneDx, Inc., Gaithersburg, MD 20877, USA.
Cara ForsterGeneDx, Inc., Gaithersburg, MD 20877, USA.
E Hallie AndrewMyelin Disorders Program, Rare Disease Institute, Children's National Hospital, Washington, DC 20010, USA.
Irina AnselmDepartment of Neurology, Boston Children's Hospital, Boston, MA 02115, USA.
Kristin W BarananoDepartment of Neurology, Johns Hopkins School of Medicine, Baltimore, MD 21287, USA.
Lauren C BriereDepartment of Medical Genetics and Metabolism, Massachusetts General Hospital, Boston, MA 02114, USA.
Julie S CohenDepartment of Neurology, Johns Hopkins School of Medicine, Baltimore, MD 21287, USA; Department of Neurology and Developmental Medicine, Division of Neurogenetics, Kennedy Krieger Institute, Baltimore, MD 21205, USA; Center for Genetic Muscle Disorders, Kennedy Krieger Institute, Baltimore, MD 21205, USA.
William J CraigenDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Cheryl CytrynbaumProgram in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.
Nina EkhilevitchThe Genetics Institute, Rambam Health Care Campus, Haifa 3109601, Israel.
Matthew J ElrickDepartment of Neurology, Johns Hopkins School of Medicine, Baltimore, MD 21287, USA.
Ali FatemiDepartment of Neurology, Johns Hopkins School of Medicine, Baltimore, MD 21287, USA; Department of Neurology and Developmental Medicine, Division of Neurogenetics, Kennedy Krieger Institute, Baltimore, MD 21205, USA; Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Jamie L FraserMyelin Disorders Program, Rare Disease Institute, Children's National Hospital, Washington, DC 20010, USA.
Renata C GallagherDepartment of Pediatrics, Division of Medical Genetics, University of California, San Francisco, CA 94158, USA.
Andrea GuerinDivision of Medical Genetics, Department of Pediatrics, Queen's University, Kingston, ON K7L 2V7, Canada.
Devon HaynesDivision of Genetics, Arnold Palmer Hospital for Children, Orlando Health, Orlando, FL 32806, USA.
Frances A HighDepartment of Medical Genetics and Metabolism, Massachusetts General Hospital, Boston, MA 02114, USA.
Cara N IngleseDivision of Clinical and Metabolic Genetics, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.
Courtney KissDivision of Medical Genetics, Department of Pediatrics, Queen's University, Kingston, ON K7L 2V7, Canada.
Mary Kay KoenigDepartment of Pediatrics, University of Texas McGovern Medical School, Houston, TX 77030, USA.
Joel KrierDivision of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
Kristin LindstromDivision of Genetics and Metabolism, Phoenix Children's Hospital, Phoenix, AZ 85016, USA.
Michael MarbleDepartment of Pediatrics, Division of Clinical Genetics and Metabolism, LSU Health Sciences Center and Children's Hospital, New Orleans, LA 70112, USA.
Hannah MeddaughDepartment of Clinical Genetics and Metabolism, Children's Hospital New Orleans, New Orleans, LA 70118, USA.
Ellen S MoranHassenfeld Children's Hospital at New York University Langone, New York University Langone Orthopedic Hospital, New York, NY 10003, USA.
Chantal F MorelFred A. Litwin Family Center in Genetic Medicine, University Health Network, Toronto, ON M5T 3L9, Canada; Department of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada.
Weiyi MuMcKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Eric A MullerClinical Genetics, Stanford Children's Health, San Francisco, CA 94109, USA.
Jessica NanceDepartment of Neurology, Johns Hopkins School of Medicine, Baltimore, MD 21287, USA; Center for Genetic Muscle Disorders, Kennedy Krieger Institute, Baltimore, MD 21205, USA.
Marvin R NatowiczInstitutes of Pathology and Laboratory Medicine and Genomic Medicine, Cleveland Clinic, Cleveland, OH 44195, USA.
Adam L NumisDepartment of Neurology and Pediatrics, University of California, San Francisco, San Francisco, CA 94158, USA.
Bridget OstremDepartment of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA.
John PappasClinical Genetic Services, Pediatrics, NYU Grossman School of Medicine, New York, NY 10016, USA.
Carl E StafstromDepartment of Neurology, Johns Hopkins School of Medicine, Baltimore, MD 21287, USA.
Haley StreffDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
David A SweetserDepartment of Medical Genetics and Metabolism, Massachusetts General Hospital, Boston, MA 02114, USA.
Marta SzybowskaFred A. Litwin Family Center in Genetic Medicine, University Health Network, Toronto, ON M5T 3L9, Canada.
Undiagnosed Diseases Network
Melissa A WalkerDepartment of Neurology, Division of Neurogenetics, Massachusetts General Hospital, Boston, MA 02114, USA.
Wei WangGeneDx, Inc., Gaithersburg, MD 20877, USA.
Karin WeissThe Genetics Institute, Rambam Health Care Campus, Haifa 3109601, Israel.
Rosanna WeksbergProgram in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Department of Pediatrics and Institute of Medical Science, University of Toronto, Toronto, ON M5G 1X8, Canada.
Patricia G WheelerDivision of Genetics, Arnold Palmer Hospital for Children, Orlando Health, Orlando, FL 32806, USA.
Grace YoonDivision of Clinical and Metabolic Genetics, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.
Robert E KingstonDepartment of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Genetics, Harvard Medical School, Boston, MA 02114, USA.
Jane JuusolaGeneDx, Inc., Gaithersburg, MD 20877, USA.
Massachusetts General Hospital · USHospital for Sick Children · CAJohns Hopkins Medicine · USBaylor College of Medicine · USChildren's National · USJohns Hopkins University · USQueen's University · CARambam Health Care Campus · ILUniversity Health Network · CAUniversity of California, San Francisco · USArnold Palmer Hospital for Children · USBoston Children's Hospital · USBrigham and Women's Hospital · USChildren's Hospital of New Orleans · USCleveland Clinic · USKennedy Krieger Institute · USLouisiana State University Health Sciences Center New Orleans · USNew York University Langone Orthopedic Hospital · USOrlando Health · USPhoenix Children's Hospital · US

Funding

The Harvard Clinical and Translational Science CenterUL1TR002541 · NCATS · HARVARD MEDICAL SCHOOL · PI NADLER, LEE MARSHALL · 2018 to 2022
$93.0M
Maintenance of Gene ExpressionR01GM043901 · NIGMS · MASSACHUSETTS GENERAL HOSPITAL · PI KINGSTON, ROBERT · 1991 to 2018
$10.7M
Center for Integrated Approaches to Undiagnosed DiseasesU01HG007690 · NHGRI · BRIGHAM AND WOMEN'S HOSPITAL · PI LOSCALZO, JOSEPH · 2014 to 2022
$10.4M
Sleep and Circadian Dysfunction, Brain and Neurobehavioral Development in AutismP50HD103538 · NICHD · HUGO W. MOSER RES INST KENNEDY KRIEGER · PI S. Ali Fatemi, Bradley L Schlaggar · 2020 to 2026
$9.9M
Functional Analysis of Epigenetic ComplexesR35GM131743 · NIGMS · MASSACHUSETTS GENERAL HOSPITAL · PI ROBERT KINGSTON · 2019 to 2026
$7.0M
NCATS NIH HHS UL1 TR002541NHGRI NIH HHS U01 HG007690NICHD NIH HHS P50 HD103538NIGMS NIH HHS R01 GM043901NIGMS NIH HHS R35 GM131743
6 · The paper itself

Abstract

MORC2 encodes an ATPase that plays a role in chromatin remodeling, DNA repair, and transcriptional regulation. Heterozygous variants in MORC2 have been reported in individuals with autosomal-dominant Charcot-Marie-Tooth disease type 2Z and spinal muscular atrophy, and the onset of symptoms ranges from infancy to the second decade of life. Here, we present a cohort of 20 individuals referred for exome sequencing who harbor pathogenic variants in the ATPase module of MORC2. Individuals presented with a similar phenotype consisting of developmental delay, intellectual disability, growth retardation, microcephaly, and variable craniofacial dysmorphism. Weakness, hyporeflexia, and electrophysiologic abnormalities suggestive of neuropathy were frequently observed but were not the predominant feature. Five of 18 individuals for whom brain imaging was available had lesions reminiscent of those observed in Leigh syndrome, and five of six individuals who had dilated eye exams had retinal pigmentary abnormalities. Functional assays revealed that these MORC2 variants result in hyperactivation of epigenetic silencing by the HUSH complex, supporting their pathogenicity. The described set of morphological, growth, developmental, and neurological findings and medical concerns expands the spectrum of genetic disorders resulting from pathogenic variants in MORC2.

Indexed as

Adenosine TriphosphatasesAdolescentAdultChildChild, PreschoolCraniofacial AbnormalitiesFemaleGenetic Diseases, InbornGrowth DisordersHeterozygoteHumansInfantIntellectual DisabilityMaleMicrocephalyMiddle AgedAdenosine TriphosphatasesMORC2 protein, humanTranscription FactorsCMT2Zdevelopmental delayintellectual disabilityLeigh-like diseasemicrocephalyMORC2

Identifiers

PMID32693025
PMCPMC7413887
OpenAlexW3042842091

What OpenQuestion holds

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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.