Evidence map›Paper›PMID 23632792›Full record

ArticleEuropean journal of human genetics : EJHG2014

Reciprocal deletion and duplication at 2q23.1 indicates a role for MBD5 in autism spectrum disorder.

Sureni V Mullegama, Jill A Rosenfeld, Carmen Orellana, Bregje W M van Bon, Sara Halbach, Elena A Repnikova, Lauren Brick, Chumei Li, Lucie Dupuis, Monica Rosello and 17 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in European journal of human genetics : EJHG, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
4.6field-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.

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

36 citing papers in PubMed, 86 citations in OpenAlex.

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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

27 authors at 15 institutions in 4 countries.

Sureni V MullegamaDepartment of Human and Molecular Genetics, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
Jill A RosenfeldSignature Genomic Laboratories, PerkinElmer Inc., Spokane, WA, USA.
Carmen OrellanaService of Genetics and Prenatal Diagnosis, University and Polytechnic Hospital La Fe, Valencia, Spain.
Bregje W M van BonDepartment of Human Genetics, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
Sara HalbachDepartment of Human Genetics, University of Chicago, Chicago, IL, USA.
Elena A RepnikovaDepartment of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, OH, USA.
Lauren BrickDepartment of Pediatrics, Clinical Genetics Program, McMaster University Medical Center and McMaster Children's Hospital, Hamilton, Ontario, Canada.
Chumei LiDepartment of Pediatrics, Clinical Genetics Program, McMaster University Medical Center and McMaster Children's Hospital, Hamilton, Ontario, Canada.
Lucie DupuisDepartment of Pediatrics, Division of Clinical and Metabolic Genetics, Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada.
Monica RoselloService of Genetics and Prenatal Diagnosis, University and Polytechnic Hospital La Fe, Valencia, Spain.
Swaroop AradhyaGeneDx, Gaithersburg, MD, USA.
D James Stavropoulos1] Cytogenetics Laboratory, Department of Pediatric Laboratory Medicine, Hospital for Sick Children, Toronto, Ontario, Canada [2] Department of Laboratory Medicine and Pathology, University of Toronto, Toronto, Ontario, Canada.
Kandamurugu ManickamDepartment of Pediatrics, Nationwide Children's Hospital, Columbus, OH, USA.
Elyse Mitchell1] Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA [2] Department of Medical Genetics, Mayo Clinic, Rochester, MN, USA.
Jennelle C Hodge1] Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA [2] Department of Medical Genetics, Mayo Clinic, Rochester, MN, USA.
Michael E Talkowski1] Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA [2] Program in Medical and Population Genetics, Broad Institute of Harvard and M.I.T., Cambridge, MA, USA [3] Departments of Genetics and Neurology, Harvard Medical School, Cambridge, MA, USA.
James F Gusella1] Program in Medical and Population Genetics, Broad Institute of Harvard and M.I.T., Cambridge, MA, USA [2] Departments of Genetics and Neurology, Harvard Medical School, Cambridge, MA, USA [3] Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA.
Kory KellerDepartment of Molecular and Medical Genetics, Child Development and Rehabilitation Center, Oregon Health and Science University, Portland, OR, USA.
Jonathan ZonanaDepartment of Molecular and Medical Genetics, Child Development and Rehabilitation Center, Oregon Health and Science University, Portland, OR, USA.
Stuart SchwartzLaboratory Corporation of America, Research Triangle Park, Durham, NC, USA.
Robert E PyattDepartment of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, OH, USA.
Darrel J WaggonerDepartment of Human Genetics, University of Chicago, Chicago, IL, USA.
Lisa G ShafferPaw Print Genetics, Genetic Veterinary Sciences, Inc., Spokane, WA, USA.
Angela E Lin1] Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA [2] Medical Genetics, Massachusetts General Hospital for Children, Boston, MA, USA.
Bert B A de VriesDepartment of Human Genetics, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
Roberto Mendoza-LondonoDepartment of Pediatrics, Division of Clinical and Metabolic Genetics, Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada.
Sarah H Elsea1] Department of Human and Molecular Genetics, Virginia Commonwealth University School of Medicine, Richmond, VA, USA [2] Department of Pediatrics, Virginia Commonwealth University School of Medicine, Richmond, VA, USA [3] Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Hospital for Sick Children · CANationwide Children's Hospital · USHospital Universitari i Politècnic La Fe · ESMayo Clinic in Arizona · USOregon Health & Science University · USRadboud University Nijmegen · NLUniversity of Chicago · USVirginia Commonwealth University · USBroad Institute · USCenter for Human Genetics · USMassachusetts General Hospital · USMcMaster Children's Hospital · CAMcMaster University · CAPerkinElmer (United States) · USTriangle · US

Funding

RAPID GENE DISCOVERYP01GM061354 · NIGMS · BRIGHAM AND WOMEN'S HOSPITAL · PI MORTON, CYNTHIA CASSON · 2001 to 2019
$24.3M
NIGMS NIH HHS P01 GM061354
6 · The paper itself

Abstract

Copy number variations associated with abnormal gene dosage have an important role in the genetic etiology of many neurodevelopmental disorders, including intellectual disability (ID) and autism. We hypothesize that the chromosome 2q23.1 region encompassing MBD5 is a dosage-dependent region, wherein deletion or duplication results in altered gene dosage. We previously established the 2q23.1 microdeletion syndrome and report herein 23 individuals with 2q23.1 duplications, thus establishing a complementary duplication syndrome. The observed phenotype includes ID, language impairments, infantile hypotonia and gross motor delay, behavioral problems, autistic features, dysmorphic facial features (pinnae anomalies, arched eyebrows, prominent nose, small chin, thin upper lip), and minor digital anomalies (fifth finger clinodactyly and large broad first toe). The microduplication size varies among all cases and ranges from 68 kb to 53.7 Mb, encompassing a region that includes MBD5, an important factor in methylation patterning and epigenetic regulation. We previously reported that haploinsufficiency of MBD5 is the primary causal factor in 2q23.1 microdeletion syndrome and that mutations in MBD5 are associated with autism. In this study, we demonstrate that MBD5 is the only gene in common among all duplication cases and that overexpression of MBD5 is likely responsible for the core clinical features present in 2q23.1 microduplication syndrome. Phenotypic analyses suggest that 2q23.1 duplication results in a slightly less severe phenotype than the reciprocal deletion. The features associated with a deletion, mutation or duplication of MBD5 and the gene expression changes observed support MBD5 as a dosage-sensitive gene critical for normal development.

Indexed as

AdolescentChildChild Development Disorders, PervasiveChild, PreschoolChromosome DeletionChromosomes, Human, Pair 2Comparative Genomic HybridizationDevelopmental DisabilitiesDNA-Binding ProteinsEpigenesis, GeneticFemaleGene DosageHumansInfantMaleTrisomyDNA-Binding ProteinsMBD5 protein, human

Identifiers

PMID23632792
PMCPMC3865402
OpenAlexW1992400870

What OpenQuestion holds

Textmetadata
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.