title: Amelogenin p.M1T and p.W4S mutations underlying hypoplastic X-linked amelogenesis imperfecta.
abstract: Mutations in the human amelogenin gene (AMELX, Xp22.3) cause a phenotypically diverse set of inherited enamel malformations. We hypothesize that the effects of specific mutations on amelogenin protein structure and expression will correlate with the enamel phenotype, clarify amelogenin structure/function relationships, and improve the clinical diagnosis of X-linked amelogenesis imperfecta (AI). We have identified two kindreds with X-linked AI and characterized the AMELX mutations underlying their AI phenotypes. The two missense mutations are both in exon 2 and affect the translation initiation codon and/or the secretion of amelogenin (p.M1T and p.W4S), resulting in hypoplastic enamel. Primary anterior teeth from affected females with the p.M1T mutation were characterized by light and scanning electron microscopy. The thin enamel had defective prism organization, and the surface was rough and pitted. Dentin was normal. The severity of the enamel phenotype correlated with the predicted effects of the mutations on amelogenin expression and secretion.
authors.affiliation: Department of Orthodontics and Pediatric Dentistry, University of Michigan Dental Research Lab, 1210 Eisenhower Place, Ann Arbor, MI 48108, USA.
authors.forename: J-W
authors.initials: JW
authors.lastname: Kim
authors.forename: J P
authors.initials: JP
authors.lastname: Simmer
authors.forename: Y Y
authors.initials: YY
authors.lastname: Hu
authors.forename: B P-L
authors.initials: BP
authors.lastname: Lin
authors.forename: C
authors.initials: C
authors.lastname: Boyd
authors.forename: J T
authors.initials: JT
authors.lastname: Wright
authors.forename: C J M
authors.initials: CJ
authors.lastname: Yamada
authors.forename: S K
authors.initials: SK
authors.lastname: Rayes
authors.forename: R J
authors.initials: RJ
authors.lastname: Feigal
authors.forename: J C-C
authors.initials: JC
authors.lastname: Hu
mesh_terms: D000567:Amelogenesis Imperfecta / Q000235:genetics*; D053523:Amelogenin; D002648:Child; D003062:Codon / Q000235:genetics; D003596:Cytosine; D003743:Dental Enamel / Q000648:ultrastructure; D003744:Dental Enamel Hypoplasia / Q000473:pathology; D003746:Dental Enamel Proteins / Q000235:genetics* / Q000378:metabolism; D003804:Dentin / Q000648:ultrastructure; D005091:Exons / Q000235:genetics; D005260:Female; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D006801:Humans; D008855:Microscopy, Electron, Scanning; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D014176:Protein Biosynthesis / Q000235:genetics; D013329:Structure-Activity Relationship; D013941:Thymine
chemical_list: C507199:AMELX protein, human; D053523:Amelogenin; D003062:Codon; D003746:Dental Enamel Proteins; D003596:Cytosine; D013941:Thymine