Dental malformations associated with biallelic MMP20 mutations
Journal
Molecular Genetics and Genomic Medicine
Journal Volume
8
Journal Issue
8
Pages
e1307
Date Issued
2020
Author(s)
Zhang H.
Chavez M.B.
Hu Y.
Seymen F.
Koruyucu M.
Kasimoglu Y.
Colvin C.D.
Kolli T.N.
Tan M.H.
Lu P.-Y.
Kim J.-W.
Foster B.L.
Bartlett J.D.
Simmer J.P.
Hu J.C.C.
Abstract
Background: Matrix metallopeptidase 20 (MMP20) is an evolutionarily conserved protease that is essential for processing enamel matrix proteins during dental enamel formation. MMP20 mutations cause human autosomal recessive pigmented hypomaturation-type amelogenesis imperfecta (AI2A2; OMIM #612529). MMP20 is expressed in both odontoblasts and ameloblasts, but its function during dentinogenesis is unclear. Methods: We characterized 10 AI kindreds with MMP20 defects, characterized human third molars and/or Mmp20?/? mice by histology, Backscattered Scanning Electron Microscopy (bSEM), ?CT, and nanohardness testing. Results: We identified six novel MMP20 disease-causing mutations. Four pathogenic variants were associated with exons encoding the MMP20 hemopexin-like (PEX) domain, suggesting a necessary regulatory function. Mutant human enamel hardness was softest (13% of normal) midway between the dentinoenamel junction (DEJ) and the enamel surface. bSEM and ?CT analyses of the third molars revealed reduced mineral density in both enamel and dentin. Dentin close to the DEJ showed an average hardness number 62%–69% of control. Characterization of Mmp20?/? mouse dentin revealed a significant reduction in dentin thickness and mineral density and a transient increase in predentin thickness, indicating disturbances in dentin matrix secretion and mineralization. Conclusion: These results expand the spectrum of MMP20 disease-causing mutations and provide the first evidence for MMP20 function during dentin formation. ? 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC
SDGs
Other Subjects
matrix metalloproteinase 20; MMP20 protein, human; allele; amelogenesis imperfecta; animal; C57BL mouse; case report; dentin; enamel; female; genetics; male; mouse; mutation; pathology; pedigree; Alleles; Amelogenesis Imperfecta; Animals; Dental Enamel; Dentin; Female; Male; Matrix Metalloproteinase 20; Mice; Mice, Inbred C57BL; Mutation; Pedigree
Publisher
Wiley-Blackwell
Type
journal article