Identification of Mutations in SLC24A4, Encoding a Potassium-Dependent Sodium/Calcium Exchanger, as a Cause of Amelogenesis Imperfecta
Identification of Mutations in SLC24A4, Encoding a Potassium-Dependent Sodium/Calcium Exchanger, as a Cause of Amelogenesis Imperfecta
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DOI：
10.1016/j.ajhg.2013.01.003
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发表时间：
2013-02-07
影响因子：
9.8
通讯作者：
Mighell, Alan J.
中科院分区：
文献类型：
--
作者：
Parry, David A.;Poulter, James A.;Mighell, Alan J.
一项结合了自身接合性定位和外显子组测序的研究发现，在一个患有低矿化成釉不全a（AI）的家族中，SLC24A4存在一个无效突变，这是一种牙釉质形成失败的疾病。SLC24A4编码成釉细胞在成釉成熟阶段上调的钙转运蛋白。进一步的AT家族的筛选确定了SLC24A4的离子结合位点中的错义突变，该错义突变预期会严重减少或消除蛋白质的离子转运功能。此外，对先前产生的Slc24a4缺失小鼠的检查鉴定了反映釉质形成受损的牙釉质中的严重缺陷。这些发现支持了SLC24A4在釉质形成过程中的钙转运中的关键作用。
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 AT 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.