Leeds Institute of Molecular Medicine, St James's University Hospital, University of Leeds, Leeds, UK.
Am J Hum Genet. 2013 Feb 7;92(2):307-12. doi: 10.1016/j.ajhg.2013.01.003. Epub 2013 Jan 31.
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.
通过自交系定位和外显子组测序相结合，在一个低矿化型牙釉质发育不全（AI）家系中发现 SLC24A4 基因的无义突变，这种情况下牙釉质形成失败。SLC24A4 基因编码在牙釉质形成的成熟阶段在成釉细胞中上调的钙转运蛋白。对进一步的 AI 家系进行筛查，发现 SLC24A4 离子结合位点的错义突变，预计会严重降低或消除该蛋白的离子转运功能。此外，对先前生成的 Slc24a4 基因缺失小鼠的检查发现，牙釉质严重缺陷反映了牙釉质形成受损。这些发现支持 SLC24A4 在牙釉质形成过程中钙转运中的关键作用。
