Metabolic Bone Disease and Genetics Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Jiao Tong University, China.
Am J Hum Genet. 2012 Jan 13;90(1):125-32. doi: 10.1016/j.ajhg.2011.11.019. Epub 2011 Dec 22.
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.
通过全外显子组测序，我们在单一致病个体的溶质载体有机阴离子转运家族成员 2A1（SLCO2A1）的内含子 1 接受位点不变 -1 位置发现了一个嘌呤到腺嘌呤的纯合转换（c.97-1G>A），该基因编码一种前列腺素转运蛋白，这是来自近亲家庭的原发性肥大性骨关节病（PHO）的致病突变。在来自两个无关非近亲家庭的另外两名患有 PHO 的患者中，我们通过 Sanger 测序鉴定出了两种不同的复合杂合突变。这些发现证实了 SLCO2A1 突变使前列腺素 E2（PGE2）的转运失活，并表明 SLCO2A1 突变是 PHO 的致病原因。此外，这项研究还可能有助于解释继发性肥大性骨关节病的病因。
