Identification of a novel dentin matrix protein-1 (DMP-1) mutation and dental anomalies in a kindred with autosomal recessive hypophosphatemia.
Identification of a novel dentin matrix protein-1 (DMP-1) mutation and dental anomalies in a kindred with autosomal recessive hypophosphatemia.
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DOI：
10.1016/j.bone.2009.09.016
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发表时间：
2010-02
期刊：
影响因子：
4.1
通讯作者：
Jueppner, Harald
中科院分区：
文献类型：
--
作者：
Turan, Serap;Aydin, Cumhur;Bereket, Abdullah;Akcay, Teoman;Gueran, Tuelay;Yaralioglu, Betul Akmen;Bastepe, Murat;Jueppner, Harald
牙本质基质蛋白-1(DMP-1)是一种非胶原性骨基质蛋白，在骨和牙齿的发育和矿化过程中起重要作用，最近发现一种常染色体隐性低磷血症(ARHP)是由DMP1基因纯合突变引起的。在这里，我们报告了一个以前没有报道的血缘关系ARHP家系，其中三个受影响的个体携带一种新的纯合子DMP-1突变。指征病例于3岁时出现双腿弯曲，因肾脏磷酸盐滞留不足而出现低磷血症。血清碱性磷酸酶活力升高，甲状旁腺素初步正常。在接受口服磷酸盐和1，25(OH)2D治疗的老年患者中，FGF23异常正常。除了FGF23水平升高外，他16个月大的弟弟和他12.5岁的表妹也有类似的临床和生化表现；三个受影响儿童的父母是一级表亲。对编码DMP-1的外显子及其侧翼内含子区域进行核苷酸序列分析。在所有受影响的个体中都发现了外显子6中一种新的纯合子移码突变(c.485Tdel；p.Glu163ArgfsX53)，导致过早停止密码子。父母和可用的未受影响的兄弟姐妹是c.485Tdel杂合子。指征病例、他的患病兄弟和表亲的牙齿生长和形状正常，但他们的恒牙和乳牙显示出扩大的牙髓室。已确定的基因突变强调了DMP-1突变在ARHP发病机制中的重要性。此外，DMP-1突变似乎通过尚不清楚的机制对牙齿发育做出贡献。
An autosomal recessive form of hypophosphatemia (ARHP) was recently shown to be caused by homozygous mutations in DMP1, the gene encoding dentin matrix protein-1 (DMP-1), a non-collagenous bone matrix protein with an important role in the development and mineralization of bone and teeth. Here, we report a previously not reported consanguineous ARHP kindred in which the three affected individuals carry a novel homozygous DMP-1 mutation. The index case presented at the age of 3 years with bowing of his legs, and showed hypophosphatemia due to insufficient renal phosphate retention. Serum alkaline phosphatase activity was elevated, with initially normal PTH. FGF23 was inappropriately normal at an older age while being treated with oral phosphate and 1,25(OH)2D. Similar clinical and biochemical findings, except for elevated FGF23 levels, were present in his 16 month-old brother and his 12.5 year-old female cousin; the parents of the three affected children are first-degree cousins. Nucleotide sequence analysis was performed on PCR-amplified exons encoding DMP-1 and flanking intronic regions. A novel homozygous frame-shift mutation (c.485Tdel; p.Glu163ArgfsX53) in exon 6 resulting in a premature stop codon was identified in all effected individuals. The parents and available unaffected siblings were heterozygous for c.485Tdel. Tooth growth and shape were normal for the index case, his affected brother and cousin, but their permanent and deciduous teeth displayed enlarged pulp chambers. The identified genetic mutation underscores the importance of DMP-1 mutations in the pathogenesis of ARHP. Furthermore, DMP-1 mutations appear to contribute, through yet unknown mechanisms, to tooth development.
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影响因子：
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作者：
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通讯作者：
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