Exome Sequencing Identifies SLCO2A1 Mutations as a Cause of Primary Hypertrophic Osteoarthropathy
Exome Sequencing Identifies SLCO2A1 Mutations as a Cause of Primary Hypertrophic Osteoarthropathy
复制标题
外显子组测序确定 SLCO2A1 突变是原发性肥厚性骨关节病的原因
DOI：
10.1016/j.ajhg.2011.11.019
复制
发表时间：
2012-01-13
影响因子：
9.8
通讯作者：
Liu, Yujuan
中科院分区：
文献类型：
--
作者：
Zhang, Zhenlin;Xia, Weibo;Liu, Yujuan
通过使用全外显子组测序，我们确定了溶质载体有机阴离子转运蛋白家族成员2A1（SLCO 2A1）中内含子1（c.97 - 1G> A）的受体位点不变-1位置处的纯合鸟嘌呤至腺嘌呤转换，该突变编码前列腺素转运蛋白，是来自一个近亲家族的原发性肥大性骨关节病（PHO）单个个体的致病突变。在另外两个受影响的个人与PHO从两个无关的非血缘关系的家庭，我们确定了两个不同的复合杂合突变，通过使用桑格测序。这些发现证实了SLCO 2A1突变抑制前列腺素E（2）（PGE（2））转运，并表明SLCO 2A1突变是PHO的致病原因。此外，本研究还有助于解释继发性肥大性骨关节病的病因。
By using whole-exome sequencing, we identified a homozygous guanine-to-adenine transition at the invariant -1 position of the acceptor site of intron 1 (c.97-1G>A) in solute carrier organic anion transporter family member 2A1 (SLCO2A1), which encodes a prostaglandin transporter protein, as the causative mutation in a single individual with primary hypertrophic osteoarthropathy (PHO) from a consanguineous family. In two other affected individuals with PHO from two unrelated nonconsanguineous families, we identified two different compound heterozygous mutations by using Sanger sequencing. These findings confirm that SLCO2A1 mutations inactivate prostaglandin E(2) (PGE(2)) transport, and they indicate that mutations in SLCO2A1 are the pathogenic cause of PHO. Moreover, this study might also help to explain the cause of secondary hypertrophic osteoarthropathy.