Novel SLCO2A1 mutations cause gender differentiated pachydermoperiostosis.
Novel SLCO2A1 mutations cause gender differentiated pachydermoperiostosis.
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新型 SLCO2A1 突变导致性别分化的厚皮骨膜增生症
DOI：
10.1530/ec-18-0326
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发表时间：
2018-08-01
影响因子：
2.9
通讯作者：
Wu Y
中科院分区：
文献类型：
--
作者：
Yuan L;Chen X;Liu Z;Wu D;Lu J;Bao G;Zhang S;Wang L;Wu Y
原发性肥大性骨关节病是一种罕见的家族性疾病，女性发病率较低。与PHO相关的基因突变已在HPGD和SLCO 2A1中被鉴定，其参与前列腺素E2代谢。在这里，我们报告了来自四个非血缘家庭的5名PHO患者。通过全外显子组测序，在两兄弟中发现了溶质载体有机阴离子转运蛋白家族成员2A1（SLCO 2A1）的两个杂合突变。桑格测序结果显示，在其他3个PHO家系中发现3个杂合突变和1个纯合突变。然而，在HPGD中没有突变。这些结果证实了SLCO 2A1纯合或复合杂合突变是PHO的致病原因。一名女性个体与她的PHO兄弟共享SLCO2A1中的相同突变，但没有任何典型的PHO症状。并对性激素在PHO发病中的作用及其意义进行了讨论。
Primary hypertrophic osteoarthropathy (PHO) is a rare familial disorder with reduced penetrance for females. The genetic mutations associated with PHO have been identified in HPGD and SLCO2A1, which involved in prostaglandin E2 metabolism. Here, we report 5 PHO patients from four non-consanguineous families. Two heterozygous mutations in solute carrier organic anion transporter family member 2A1 (SLCO2A1) were identified in two brothers by whole-exome sequencing. Three heterozygous mutations and one homozygous mutation were identified in other three PHO families by Sanger sequencing. However, there was no mutation in HPGD. These findings confirmed that homozygous or compound heterozygous mutations of SLCO2A1 were the pathogenic cause of PHO. A female individual shared the same mutations in SLCO2A1 with her PHO brother but did not have any typical PHO symptoms. The influence of sex hormones on the pathogenesis of PHO and its implication were discussed.