A CCR4-NOT Transcription Complex, Subunit 1, CNOT1, Variant Associated with Holoprosencephaly.


Journal

American journal of human genetics
ISSN: 1537-6605
Titre abrégé: Am J Hum Genet
Pays: United States
ID NLM: 0370475

Informations de publication

Date de publication:
02 05 2019
Historique:
received: 07 12 2018
accepted: 18 03 2019
pubmed: 23 4 2019
medline: 7 2 2020
entrez: 23 4 2019
Statut: ppublish

Résumé

Holoprosencephaly is the incomplete separation of the forebrain during embryogenesis. Both genetic and environmental etiologies have been determined for holoprosencephaly; however, a genetic etiology is not found in most cases. In this report, we present two unrelated individuals with semilobar holoprosencephaly who have the identical de novo missense variant in the gene CCR4-NOT transcription complex, subunit 1 (CNOT1). The variant (c.1603C>T [p.Arg535Cys]) is predicted to be deleterious and is not present in public databases. CNOT1 has not been previously associated with holoprosencephaly or other brain malformations. In situ hybridization analyses of mouse embryos show that Cnot1 is expressed in the prosencephalic neural folds at gestational day 8.25 during the critical period for subsequent forebrain division. Combining human and mouse data, we show that CNOT1 is associated with incomplete forebrain division.

Identifiants

pubmed: 31006510
pii: S0002-9297(19)30113-2
doi: 10.1016/j.ajhg.2019.03.017
pmc: PMC6506867
pii:
doi:

Substances chimiques

CNOT1 protein, human 0
Transcription Factors 0

Types de publication

Case Reports Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

990-993

Subventions

Organisme : NIEHS NIH HHS
ID : R01 ES026819
Pays : United States
Organisme : NIEHS NIH HHS
ID : T32 ES007015
Pays : United States

Informations de copyright

Published by Elsevier Inc.

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Auteurs

Paul Kruszka (P)

Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Seth I Berger (SI)

Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA; Rare Disease Institute, Genetics and Metabolism, Children's National Health System, Washington, DC 20036, USA.

Karin Weiss (K)

Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Joshua L Everson (JL)

Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53706, USA; Molecular and Environmental Toxicology Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53706, USA.

Ariel F Martinez (AF)

Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Sungkook Hong (S)

Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Kwame Anyane-Yeboa (K)

Division of Clinical Genetics, Department of Pediatrics, Columbia University Medical Center, New York, NY 10032, USA.

Robert J Lipinski (RJ)

Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53706, USA; Molecular and Environmental Toxicology Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53706, USA.

Maximilian Muenke (M)

Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: mamuenke@mail.nih.gov.

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Classifications MeSH