title: Mutation of the gene encoding the enamel-specific protein, enamelin, causes autosomal-dominant amelogenesis imperfecta.
abstract: Amelogenesis imperfecta (AI) is a group of inherited defects of dental enamel formation that shows both clinical and genetic heterogeneity. To date, mutations in the gene encoding amelogenin have been shown to underlie a subset of the X-linked recessive forms of AI. Although none of the genes underlying autosomal-dominant or autosomal-recessive AI have been identified, a locus for a local hypoplastic form has been mapped to human chromosome 4q11-q21. In the current investigation, we have analysed a family with an autosomal-dominant, smooth hypoplastic form of AI. Our results have shown that a splicing mutation in the splice donor site of intron 7 of the gene encoding the enamel-specific protein enamelin underlies the phenotype observed in this family. This is the first autosomal-dominant form of AI for which the genetic mutation has been identified. As this type of AI is clinically distinct from that localized previously to chromosome 4q11-q21, these findings highlight the need for a molecular classification of this group of disorders.
authors.affiliation: School of Biological Sciences and Department of Dental Medicine and Surgery, 3.239 Stopford Building, University of Manchester, Oxford Road, Manchester M13 9PT, UK.
authors.forename: M H
authors.initials: MH
authors.lastname: Rajpar
authors.forename: K
authors.initials: K
authors.lastname: Harley
authors.forename: C
authors.initials: C
authors.lastname: Laing
authors.forename: R M
authors.initials: RM
authors.lastname: Davies
authors.forename: M J
authors.initials: MJ
authors.lastname: Dixon
mesh_terms: D000567:Amelogenesis Imperfecta / Q000235:genetics*; D002894:Chromosomes, Human, Pair 4; D003746:Dental Enamel Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D003746:Dental Enamel Proteins; C038456:tuftelin