Parry, DA, Smith, CEL orcid.org/0000-0001-8320-5105, El-Sayed, W et al. (17 more authors) (2016) Mutations in the pH-Sensing G-protein-Coupled Receptor GPR68 Cause Amelogenesis Imperfecta. American Journal of Human Genetics, 99 (4). pp. 984-990. ISSN 0002-9297
Abstract
Amelogenesis is the process of dental enamel formation, leading to the deposition of the hardest tissue in the human body. This process requires the intricate regulation of ion transport and controlled changes to the developing enamel matrix pH. The means by which the enamel organ regulates pH during amelogenesis is largely unknown. We identified rare homozygous variants in GPR68 in three families with Amelogenesis Imperfecta, a genetically and phenotypically heterogeneous group of inherited conditions associated with abnormal enamel formation. Each of these homozygous variants (a large in-frame deletion, a frameshift deletion and a missense) were predicted to result in loss of function. GPR68 encodes a proton sensing G-protein-coupled receptor with sensitivity in the pH range that occurs in the developing enamel matrix during amelogenesis. Immunohistochemistry of rat mandibles confirmed localisation of GPR68 in the enamel organ at all stages of amelogenesis. Our data identify a role for GPR68 as a proton sensor that is required for proper enamel formation.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2016 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
Keywords: | Amelogenesis imperfecta; pH sensing; amelogenesis; teeth; GPR68 |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Dentistry (Leeds) > Oral Surgery (Leeds) The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Institute of Rheumatology & Musculoskeletal Medicine (LIRMM) (Leeds) > Inflammatory Arthritis (Leeds) |
Funding Information: | Funder Grant number Wellcome Trust 093113/A/10/Z |
Depositing User: | Symplectic Publications |
Date Deposited: | 05 Sep 2016 11:58 |
Last Modified: | 28 Aug 2020 10:17 |
Published Version: | https://dx.doi.org/10.1016/j.ajhg.2016.08.020 |
Status: | Published |
Publisher: | Cell Press |
Identification Number: | 10.1016/j.ajhg.2016.08.020 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:104234 |