Novel Ameloblastin Variants, Contrasting Amelogenesis Imperfecta Phenotypes.

Autor:	Hany U; Leeds Institute of Medical Research, University of Leeds, St. James's University Hospital, Leeds, UK., Watson CM; Leeds Institute of Medical Research, University of Leeds, St. James's University Hospital, Leeds, UK.; North East and Yorkshire Genomic Laboratory Hub, Central Lab, St. James's University Hospital, Leeds, UK., Liu L; Leeds Institute of Medical Research, University of Leeds, St. James's University Hospital, Leeds, UK.; School of Dentistry, Clarendon Way, University of Leeds, Leeds, UK., Nikolopoulos G; Leeds Institute of Medical Research, University of Leeds, St. James's University Hospital, Leeds, UK., Smith CEL; Leeds Institute of Medical Research, University of Leeds, St. James's University Hospital, Leeds, UK., Poulter JA; Leeds Institute of Medical Research, University of Leeds, St. James's University Hospital, Leeds, UK., Brown CJ; Birmingham Dental Hospital, Mill Pool Way, Edgbaston, Birmingham, UK., Patel A; LCRN West Midlands Core Team, NIHR Clinical Research Network (CRN), Birmingham Research Park (West Wing), Edgbaston, Birmingham, UK., Rodd HD; Academic Unit of Oral Health Dentistry and Society, School of Clinical Dentistry, University of Sheffield, Sheffield, S Yorks, UK., Balmer R; School of Dentistry, Clarendon Way, University of Leeds, Leeds, UK., Harfoush A; School of Dentistry, Clarendon Way, University of Leeds, Leeds, UK., Al-Jawad M; School of Dentistry, Clarendon Way, University of Leeds, Leeds, UK., Inglehearn CF; Leeds Institute of Medical Research, University of Leeds, St. James's University Hospital, Leeds, UK., Mighell AJ; School of Dentistry, Clarendon Way, University of Leeds, Leeds, UK.
Jazyk:	angličtina
Zdroj:	Journal of dental research [J Dent Res] 2024 Jan; Vol. 103 (1), pp. 22-30. Date of Electronic Publication: 2023 Dec 06.
DOI:	10.1177/00220345231203694
Abstrakt:	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. Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu