Nikolopoulos, G orcid.org/0000-0003-3166-8372, Smith, CEL orcid.org/0000-0001-8320-5105, Poulter, JA orcid.org/0000-0003-2048-5693 et al. (10 more authors) (2021) Spectrum of pathogenic variants and founder effects in amelogenesis imperfecta associated with MMP20. Human Mutation, 42 (5). pp. 567-576. ISSN 1059-7794
Abstract
Amelogenesis imperfecta (AI) describes a heterogeneous group of developmental enamel defects that typically have Mendelian inheritance. Exome sequencing of 10 families with recessive hypomaturation AI revealed four novel and one known variants in the matrix metallopeptidase 20 (MMP20) gene that were predicted to be pathogenic. MMP20 encodes a protease that cleaves the developing extracellular enamel matrix and is necessary for normal enamel crystal growth during amelogenesis. New homozygous missense changes were shared between four families of Pakistani heritage (c.625G>C; p.(Glu209Gln)) and two of Omani origin (c.710C>A; p.(Ser237Tyr)). In two families of UK origin and one from Costa Rica, affected individuals were homozygous for the previously reported c.954-2A>T; p.(Ile319Phefs*19) variant. For each of these variants, microsatellite haplotypes appeared to exclude a recent founder effect, but elements of haplotype were conserved, suggesting more distant founding ancestors. New compound heterozygous changes were identified in one family of the European heritage: c.809_811+12delinsCCAG; p.(?) and c.1122A>C; p.(Gln374His). This report further elucidates the mutation spectrum of MMP20 and the probable impact on protein function, confirms a consistent hypomaturation phenotype and shows that mutations in MMP20 are a common cause of autosomal recessive AI in some communities.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2021 The Authors. This is an open access article under the terms of the Creative Commons Attribution 4.0 International License (CC BY 4.0) (https://creativecommons.org/licenses/by/4.0/) |
Keywords: | amelogenesis imperfecta, enamel, founder effect, hypomaturation AI, MMP20 |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Engineering & Physical Sciences (Leeds) > School of Physics and Astronomy (Leeds) > Theoretical Physics (Leeds) The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biology (Leeds) 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 Dentistry (Leeds) > Paediatric Dentistry (Leeds) |
Funding Information: | Funder Grant number Wellcome Trust 093113/A/10/Z |
Depositing User: | Symplectic Publications |
Date Deposited: | 01 Dec 2021 13:20 |
Last Modified: | 28 Feb 2025 14:43 |
Status: | Published |
Publisher: | Wiley |
Identification Number: | 10.1002/humu.24187 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:180540 |