Grey, William George orcid.org/0000-0001-8209-5645, Izatt, Louise, Saharaoui, Wafa et al. (6 more authors) (2013) Deficiency of the cyclin-dependent kinase inhibitor, CDKN1B, results in overgrowth and neurodevelopmental delay. Human Mutation. pp. 864-868. ISSN 1098-1004
Abstract
Germline mutations in the cyclin-dependent kinase inhibitor, CDKN1B, have been described in patients with multiple endocrine neoplasia (MEN), a cancer predisposition syndrome with adult onset neoplasia and no additional phenotypes. Here, we describe the first human case of CDKN1B deficiency, which recapitulates features of the murine CDKN1B knockout mouse model, including gigantism and neurodevelopmental defects. Decreased mRNA and protein expression of CDKN1B were confirmed in the proband's peripheral blood, which is not seen in MEN syndrome patients. We ascribed the decreased protein level to a maternally derived deletion on chromosome 12p13 encompassing the CDKN1B locus (which reduced mRNA expression) and a de novo allelic variant (c.-73G>A) in the CDKN1B promoter (which reduced protein translation). We propose a recessive model where decreased dosage of CDKN1B during development in humans results in a neuronal phenotype akin to that described in mice, placing CDKN1B as a candidate gene involved in developmental delay.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Biology (York) |
Depositing User: | Pure (York) |
Date Deposited: | 14 Jan 2022 12:50 |
Last Modified: | 30 Dec 2024 00:15 |
Published Version: | https://doi.org/10.1002/humu.22314 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1002/humu.22314 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:182560 |
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Description: Human Mutation - 2013 - Grey - Deficiency of the Cyclin‐Dependent Kinase Inhibitor CDKN1B Results in Overgrowth and
Licence: CC-BY 2.5