title: Identification of mutations in SLC24A4, encoding a potassium-dependent sodium/calcium exchanger, as a cause of amelogenesis imperfecta.
abstract: A combination of autozygosity mapping and exome sequencing identified a null mutation in SLC24A4 in a family with hypomineralized amelogenesis imperfect a (AI), a condition in which tooth enamel formation fails. SLC24A4 encodes a calcium transporter upregulated in ameloblasts during the maturation stage of amelogenesis. Screening of further AI families identified a missense mutation in the ion-binding site of SLC24A4 expected to severely diminish or abolish the ion transport function of the protein. Furthermore, examination of previously generated Slc24a4 null mice identified a severe defect in tooth enamel that reflects impaired amelogenesis. These findings support a key role for SLC24A4 in calcium transport during enamel formation.
authors: Leeds Institute of Molecular Medicine, St James's University Hospital, University of Leeds, Leeds, UK.
authors: David A
authors: DA
authors: Parry
authors: James A
authors: JA
authors: Poulter
authors: Clare V
authors: CV
authors: Logan
authors: Steven J
authors: SJ
authors: Brookes
authors: Hussain
authors: H
authors: Jafri
authors: Christopher H
authors: CH
authors: Ferguson
authors: Babra M
authors: BM
authors: Anwari
authors: Yasmin
authors: Y
authors: Rashid
authors: Haiqing
authors: H
authors: Zhao
authors: Colin A
authors: CA
authors: Johnson
authors: Chris F
authors: CF
authors: Inglehearn
authors: Alan J
authors: AJ
authors: Mighell
mesh_terms: D000567:Amelogenesis Imperfecta / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D017920:Antiporters / Q000737:chemistry / Q000235:genetics*; D001483:Base Sequence; D005190:Family; D005260:Female; D006801:Humans; D007180:Incisor / Q000648:ultrastructure; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D019831:Sodium-Calcium Exchanger / Q000235:genetics*
chemical_list: D017920:Antiporters; C470570:SLC24A4 protein, human; C569957:Slc24a4 protein, mouse; D019831:Sodium-Calcium Exchanger; C074530:potassium-dependent sodium-calcium exchanger
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