ArticleAmerican journal of human genetics2017
A Recurrent De Novo Variant in NACC1 Causes a Syndrome Characterized by Infantile Epilepsy, Cataracts, and Profound Developmental Delay.
Registry-linked trialOpen access · bronzeAbstract readCase Reports
In one paragraph
Article in American journal of human genetics, 2017. 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 35 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed, 1 pooled it
4.4field-weighted citation impact, top 6% of its field
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.
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.
Clinical and Genetic Evaluation of Patients With Undiagnosed Disorders Through the Undiagnosed Diseases Network
Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- MicroRNAs signatures as potential molecular markers in mild cognitive impairment: a meta-analysis.Frontiers in aging neuroscience · 2024Pooled it
- From Suspected Congenital Cytomegalovirus Infection to Malan Syndrome: Delayed Genetic Diagnosis Due to Diagnostic Anchoring.Diseases (Basel, Switzerland) · 2026Article
- Pharmacogenetics of anti-seizure medications in Arab countries: a comprehensive review.Future science OA · 2025Review
- Unraveling the molecular landscape of congenital pseudoarthrosis of the tibia: insights from a comprehensive analysis of 159 probands.Orphanet journal of rare diseases · 2025Article
- NACC1 accelerates the progression of AML by regulating the ADAM9/PI3K/AKT axis.International journal of medical sciences · 2025Article
- Loss-of-function of the Zinc Finger Homeobox 4 (medRxiv : the preprint server for health sciences · 2024Article
- Hyperkinetic Movement Disorder Caused by the Recurrent c.892C>T NACC1 Variant.Movement disorders clinical practice · 2024Article
- Nacc1 Mutation in Mice Models Rare Neurodevelopmental Disorder with Underlying Synaptic Dysfunction.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Case report: A novelFrontiers in psychiatry · 2024Article
- Parental perspectives of episodic irritability in an ultra-rare genetic disorder associated with NACC1.Orphanet journal of rare diseases · 2023Article
- Knockout mouse models as a resource for the study of rare diseases.Mammalian genome : official journal of the International Mammalian Genome Society · 2023Article
- Familial and syndromic forms of arachnoid cyst implicate genetic factors in disease pathogenesis.Cerebral cortex (New York, N.Y. : 1991) · 2023Article
- An intellectual-disability-associated mutation of the transcriptional regulatorFrontiers in molecular neuroscience · 2023Review
- Epigenetic genes and epilepsy - emerging mechanisms and clinical applications.Nature reviews. Neurology · 2022Review
- Massive Loss of Transcription Factors Promotes the Initial Diversification of Placental Mammals.International journal of molecular sciences · 2022Article
- MiR-361-3p alleviates cerebral ischemia-reperfusion injury by targeting NACC1 through the PINK1/Parkin pathway.Journal of molecular histology · 2022Article
- Article
- Identifying digenic disease genes via machine learning in the Undiagnosed Diseases Network.American journal of human genetics · 2021Article
- Rare disease patient matchmaking: development and outcomes of an internet case-finding strategy in the Undiagnosed Diseases Network.Orphanet journal of rare diseases · 2021Article
- Model organisms contribute to diagnosis and discovery in the undiagnosed diseases network: current state and a future vision.Orphanet journal of rare diseases · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
42 authors at 14 institutions in 3 countries.
Kelly SchochDivision of Medical Genetics, Department of Pediatrics, Duke Health, Durham, NC 27710, USA.
Linyan MengDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Baylor Genetics, Houston, TX 77021, USA.
Szabolcs SzelingerDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
David R BeardenDivision of Child Neurology, Department of Neurology, University of Rochester School of Medicine, Rochester, NY 14627, USA.
Asbjorg Stray-PedersenBaylor-Hopkins Center for Mendelian Genomics, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Norwegian National Unit for Newborn Screening, Oslo University Hospital, 0424 Oslo, Norway.
Oyvind L BuskSection of Medical Genetics, Department of Laboratory Medicine, Telemark Hospital, 3710 Skien, Norway.
Nicholas StongInstitute for Genomic Medicine, Columbia University, New York, NY 10032, USA.
Eriskay ListonDivision of Clinical and Metabolic Genetics, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.
Ronald D CohnDivision of Clinical and Metabolic Genetics, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Department of Pediatrics, University of Toronto, Toronto, ON M5G 1X8, Canada.
Fernando ScagliaDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Texas Children's Hospital, Houston, TX 77030, USA.
Jill A RosenfeldDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Jennifer TarpinianDivision of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Cara M SkrabanDivision of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Roberts Individualized Medical Genetics Center, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Pediatrics, The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Matthew A DeardorffDivision of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Roberts Individualized Medical Genetics Center, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Pediatrics, The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Jeremy N FriedmanDepartment of Pediatrics, University of Toronto, Toronto, ON M5G 1X8, Canada.
Zeynep Coban AkdemirNorwegian National Unit for Newborn Screening, Oslo University Hospital, 0424 Oslo, Norway.
Nicole WalleyDivision of Medical Genetics, Department of Pediatrics, Duke Health, Durham, NC 27710, USA.
Mohamad A MikatiDivision of Pediatric Neurology, Department of Pediatrics, Duke Health, Durham, NC 27710, USA.
Peter G KranzDivision of Neuroradiology, Department of Radiology, Duke Health, Durham, NC 27710, USA.
Joan JasienDivision of Pediatric Neurology, Department of Pediatrics, Duke Health, Durham, NC 27710, USA.
Allyn McConkie-RosellDivision of Medical Genetics, Department of Pediatrics, Duke Health, Durham, NC 27710, USA.
Marie McDonaldDivision of Medical Genetics, Department of Pediatrics, Duke Health, Durham, NC 27710, USA.
Stephanie Burns WechslerDivision of Medical Genetics, Department of Pediatrics, Duke Health, Durham, NC 27710, USA; Division of Cardiology, Department of Pediatrics, Duke Health, Durham, NC 27710, USA.
Michael FreemarkDivision of Pediatric Endocrinology and Diabetes, Department of Pediatrics, Duke Health, Durham, NC 27710, USA.
Sujay KansagraDivision of Pediatric Neurology, Department of Pediatrics, Duke Health, Durham, NC 27710, USA.
Sharon FreedmanDuke Eye Center, Duke Health, Durham, NC 27710, USA.
Deeksha BaliDepartment of Pathology, Duke Health, Durham, NC 27710, USA.
Francisca MillanGeneDx, Gaithersburg, MD 20877, USA.
Sherri BaleGeneDx, Gaithersburg, MD 20877, USA.
Stanley F NelsonDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Hane LeeDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Clinical Genomics Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Naghmeh DorraniClinical Genomics Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
UCLA Clinical Genomics Center
Undiagnosed Diseases Network
David B GoldsteinInstitute for Genomic Medicine, Columbia University, New York, NY 10032, USA.
Rui XiaoDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Baylor Genetics, Houston, TX 77021, USA.
Yaping YangDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Baylor Genetics, Houston, TX 77021, USA.
Jennifer E PoseyDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Baylor-Hopkins Center for Mendelian Genomics, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Julian A Martinez-AgostoClinical Genomics Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
James R LupskiDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Baylor-Hopkins Center for Mendelian Genomics, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA; Texas Children's Hospital, Houston, TX 77030, USA.
Michael F WanglerDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Baylor-Hopkins Center for Mendelian Genomics, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Neurological Research Institute, Texas Children's Hospital, Houston, TX 77030, USA. Electronic address: michael.wangler@bcm.edu.
Vandana ShashiDivision of Medical Genetics, Department of Pediatrics, Duke Health, Durham, NC 27710, USA. Electronic address: vandana.shashi@duke.edu.
University of California, Los Angeles · USDuke Medical Center · USBaylor College of Medicine · USBaylor Genetics · USColumbia University · USDuke University Health System · USUniversity of Pennsylvania · USChildren's Hospital of Philadelphia · USTexas Children's Hospital · USUniversity of Rochester · USUniversity of Toronto · CAHospital for Sick Children · CAOslo University Hospital · NOTelemark Hospital · NO
Funding
UCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0MUnderstanding Repetitive Behavior in AutismP50HD055784 · NICHD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BOOKHEIMER, SUSAN Y · 2007 to 2021
$32.0MBaylor-Johns Hopkins Center for Mendelian GeneticsUM1HG006542 · NHGRI · JOHNS HOPKINS UNIVERSITY · PI VALLE, DAVID · 2016 to 2020
$14.5MAn integrated and diverse genomic medicine program for undiagnosed diseasesU01HG007672 · NHGRI · DUKE UNIVERSITY · PI SHASHI, VANDANA · 2014 to 2022
$13.4MZebrafish CoreU54NS093793 · NINDS · BAYLOR COLLEGE OF MEDICINE · PI BELLEN, HUGO J · 2015 to 2022
$7.5MGenomic medicine and gene function implementation for an underserved populationR01HG011795 · NHGRI · BAYLOR COLLEGE OF MEDICINE · PI BELLEN, HUGO J, WANGLER, MICHAEL FRANCIS · 2021 to 2025
$4.8MNCATS NIH HHS UL1 TR000124NHGRI NIH HHS R01 HG011795NHGRI NIH HHS U01 HG007672NHGRI NIH HHS UM1 HG006542NICHD NIH HHS P50 HD055784NINDS NIH HHS U54 NS093793
Abstract
Whole-exome sequencing (WES) has increasingly enabled new pathogenic gene variant identification for undiagnosed neurodevelopmental disorders and provided insights into both gene function and disease biology. Here, we describe seven children with a neurodevelopmental disorder characterized by microcephaly, profound developmental delays and/or intellectual disability, cataracts, severe epilepsy including infantile spasms, irritability, failure to thrive, and stereotypic hand movements. Brain imaging in these individuals reveals delay in myelination and cerebral atrophy. We observe an identical recurrent de novo heterozygous c.892C>T (p.Arg298Trp) variant in the nucleus accumbens associated 1 (NACC1) gene in seven affected individuals. One of the seven individuals is mosaic for this variant. NACC1 encodes a transcriptional repressor implicated in gene expression and has not previously been associated with germline disorders. The probability of finding the same missense NACC1 variant by chance in 7 out of 17,228 individuals who underwent WES for diagnoses of neurodevelopmental phenotypes is extremely small and achieves genome-wide significance (p = 1.25 × 10
Indexed as
Genetic VariationAllelesAmino Acid SequenceBrainCataractChildChild, PreschoolFemaleGenome-Wide Association StudyHumansInfantIntellectual DisabilityMagnetic Resonance ImagingMaleMicrocephalyMutation, MissenseNACC1 protein, humanNeoplasm ProteinsRepressor Proteinscataractsdevelopmental/intellectual disabilitiesepilepsyirritabilitymicrocephalyNACC1stereotypywhole-exome sequencing
Identifiers
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Registered trials
NCT02450851ClinicalTrials.gov
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.