Yuan Lijuan, Chen Xihui, Liu Ziyu, Wu Dan, Lu Jianguo, Bao Guoqiang, Zhang Sijia, Wang Lifeng, Wu Yuanming
Department of Biochemistry and Molecular Biology, Center for DNA Typing, Air Force Medical University, Xi'an, Shaanxi, People's Republic of China.
Department of General Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, Shaanxi, People's Republic of China.
Endocr Connect. 2018 Nov;7(11):1116-1128. doi: 10.1530/EC-18-0326.
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.
原发性肥厚性骨关节病（PHO）是一种罕见的家族性疾病，女性的发病率较低。与PHO相关的基因突变已在参与前列腺素E2代谢的HPGD和SLCO2A1中被发现。在此，我们报告了来自四个非近亲家庭的5例PHO患者。通过全外显子测序在两兄弟中发现了溶质载体有机阴离子转运体家族成员2A1（SLCO2A1）的两个杂合突变。通过桑格测序在其他三个PHO家族中发现了三个杂合突变和一个纯合突变。然而，HPGD中未发现突变。这些发现证实，SLCO2A1的纯合或复合杂合突变是PHO的致病原因。一名女性个体与她患PHO的兄弟在SLCO2A1中具有相同的突变，但没有任何典型的PHO症状。讨论了性激素对PHO发病机制的影响及其意义。
