Hany, U. orcid.org/0000-0002-4486-1625, Watson, C.M. orcid.org/0000-0003-2371-1844, Liu, L. et al. (11 more authors) (2024) Novel ameloblastin variants, contrasting amelogenesis imperfecta phenotypes. Journal of Dental Research, 103 (1). pp. 22-30. ISSN 0022-0345
Abstract
Amelogenesis imperfecta (AI) comprises a group of rare, inherited disorders with abnormal enamel formation. Ameloblastin (AMBN), the second most abundant enamel matrix protein (EMP), plays a critical role in amelogenesis. Pathogenic biallelic loss-of-function AMBN variants are known to cause recessive hypoplastic AI. A report of a family with dominant hypoplastic AI attributed to AMBN missense change p.Pro357Ser, together with data from animal models, suggests that the consequences of AMBN variants in human AI remain incompletely characterized. Here we describe 5 new pathogenic AMBN variants in 11 individuals with AI. These fall within 3 groups by phenotype. Group 1, consisting of 6 families biallelic for combinations of 4 different variants, have yellow hypoplastic AI with poor-quality enamel, consistent with previous reports. Group 2, with 2 families, appears monoallelic for a variant shared with group 1 and has hypomaturation AI of near-normal enamel volume with pitting. Group 3 includes 3 families, all monoallelic for a fifth variant, which are affected by white hypoplastic AI with a thin intact enamel layer. Three variants, c.209C>G; p.(Ser70*) (groups 1 and 2), c.295T>C; p.(Tyr99His) (group 1), and c.76G>A; p.(Ala26Thr) (group 3) were identified in multiple families. Long-read AMBN locus sequencing revealed these variants are on the same conserved haplotype, implying they originate from a common ancestor. Data presented therefore provide further support for possible dominant as well as recessive inheritance for AMBN-related AI and for multiple contrasting phenotypes. In conclusion, our findings suggest pathogenic AMBN variants have a more complex impact on human AI than previously reported.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2023 International Association for Dental, Oral, and Craniofacial Research and American Association for Dental, Oral, and Craniofacial Research. This article is distributed under the terms of the Creative Commons Attribution 4.0 License (https://creativecommons.org/licenses/by/4.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is properly attributed. |
Keywords: | AMBN; X-ray microtomography; amelogenesis; dental enamelhypoplastic AI; founder effect; Animals; Humans; Amelogenesis Imperfecta; Phenotype; Amelogenesis; Dental Enamel Proteins; Pedigree |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Clinical Dentistry (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 05 Jan 2024 16:55 |
Last Modified: | 05 Jan 2024 16:55 |
Status: | Published |
Publisher: | SAGE Publications |
Refereed: | Yes |
Identification Number: | 10.1177/00220345231203694 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:207087 |