title: Altered enamelin phosphorylation site causes amelogenesis imperfecta.
abstract: Defects in the enamelin gene (ENAM) cause amelogenesis imperfecta (AI). Our objective was to identify the genetic etiology of enamel hypoplasia in a Caucasian proband. Our hypothesis was that ENAM was defective. The proband and his father have an AG insertion (g.13185_13186insAG; p.422FsX448) in ENAM previously identified in AI kindreds from Slovenia and Turkey. The proband, his brother, and his mother have a novel missense mutation (g.12573C>T) that substitutes leucine for a phosphorylated serine (p.S216L) in the 32-kDa enamelin cleavage product. In this family, a defect in one ENAM allele caused minor pitting or localized enamel hypoplasia, whereas defects in both alleles caused severe enamel malformations, with little or no mineral covering dentin. Ser(216) is one of two serines on the 32-kDa enamelin that is phosphorylated by Golgi casein kinase and is thought to mediate calcium binding. We propose that phosphorylation of enamelin is critical for its function.
authors.affiliation: Department of Biologic and Materials Sciences, University of Michigan School of Dentistry, 1011 N. University, Ann Arbor, MI 48109-1078, USA.
authors.forename: H-C
authors.initials: HC
authors.lastname: Chan
authors.forename: L
authors.initials: L
authors.lastname: Mai
authors.forename: A
authors.initials: A
authors.lastname: Oikonomopoulou
authors.forename: H L
authors.initials: HL
authors.lastname: Chan
authors.forename: A S
authors.initials: AS
authors.lastname: Richardson
authors.forename: S-K
authors.initials: SK
authors.lastname: Wang
authors.forename: J P
authors.initials: JP
authors.lastname: Simmer
authors.forename: J C-C
authors.initials: JC
authors.lastname: Hu
mesh_terms: D000225:Adenine; D000483:Alleles; D000567:Amelogenesis Imperfecta / Q000235:genetics*; D000595:Amino Acid Sequence / Q000235:genetics; D002118:Calcium / Q000378:metabolism; D047388:Casein Kinases / Q000378:metabolism; D003596:Cytosine; D003744:Dental Enamel Hypoplasia / Q000235:genetics*; D003746:Dental Enamel Proteins / Q000235:genetics*; D005091:Exons / Q000235:genetics; D016368:Frameshift Mutation / Q000235:genetics; D006056:Golgi Apparatus / Q000378:metabolism; D006147:Guanine; D006801:Humans; D007930:Leucine / Q000235:genetics; D008297:Male; D016254:Mutagenesis, Insertional / Q000235:genetics; D020125:Mutation, Missense / Q000235:genetics; D010375:Pedigree; D010766:Phosphorylation; D017384:Sequence Deletion / Q000235:genetics; D012694:Serine / Q000235:genetics; D013941:Thymine; D055815:Young Adult
chemical_list: D003746:Dental Enamel Proteins; C038456:tuftelin; D012694:Serine; D006147:Guanine; D003596:Cytosine; D047388:Casein Kinases; D007930:Leucine; D000225:Adenine; D013941:Thymine; D002118:Calcium