Role of Prostaglandin E-Major Urinary Metabolite Levels in Identifying the Phenotype of Pachydermoperiostosis
Role of Prostaglandin E-Major Urinary Metabolite Levels in Identifying the Phenotype of Pachydermoperiostosis
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前列腺素 E 主要尿液代谢物水平在识别厚皮骨膜增生症表型中的作用
DOI：
10.1016/j.jid.2021.04.025
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发表时间：
2021
影响因子：
6.5
通讯作者：
Kabashima Kenji
中科院分区：
文献类型：
--
作者：
Ishibashi Mami;Oiwa Tomohiro;Nomura Takashi;Yoshikawa Yoshiaki;Niizeki Hironori;Kabashima Kenji
厚皮性骨膜增生症（PDP）是一种常染色体隐性遗传性疾病，其具有三个诊断特征：趾杵状、骨膜增生和厚皮症，包括回状垂直皮肤（CVG）（Castori等人，2005年）。CVG是一种肥厚的头皮皮肤褶皱产生脑状外观的疾病。PDP的表型谱已被分为三种不同的形式。首先，完整的表格涉及所有三个主要症状，包括CVG。第二，不完全形式具有所有三种症状，但仅缺乏CVG。第三，截头形显示主要的厚皮症和最小的骨膜增生（Castori等人，2005).已经鉴定了两种致病基因-HPGD和SLCO 2A 1-分别编码15-羟基前列腺素脱氢酶和溶质载体有机阴离子转运蛋白家族成员2A 1（SLCO 2A 1）（Diggle等人，2012; Uppal等人，2008; Zhang等人，2012年）。前列腺素E2（PGE 2）由环氧合酶合成，代谢成稳定的前列腺素E-主要尿代谢物（PGE-MUM），并最终以PGE-MUM的形式在尿中排泄（Hamberg et al.，1971年）。由SLCO 2A 1输入的PGE 2被细胞质15-羟基前列腺素脱氢酶迅速氧化。据推测，这些基因中的任一个的功能障碍引起PGE 2水平的增加（Sasaki等人，2012年）。两个先驱小组提出，具有SLCO 2A 1突变的受影响个体具有升高的尿PGE 2;与HPGD缺陷患者相反，他们还排泄大量的PGE 2代谢物PGE-M（Diggle等人，2012; Zhang等人，2012年）。
Pachydermoperiostosis (PDP) is an autosomal recessive hereditary disease that has three diagnostic features: digital clubbing, periostosis, and pachydermia, including cutis verticis gyrata (CVG)(Castori et al., 2005). CVG is a condition in which folds of the hypertrophic scalp skin create a cerebriform appearance. The phenotypic spectrum of PDP has been categorized into three distinct forms. First, the complete form involves all the three major symptoms, including CVG. Second, the incomplete form has all the three symptoms but solely lacks CVG. Third, the fruste form shows predominant pachydermia and minimal periostosis (Castori et al., 2005).Two causative genes—HPGD and SLCO2A1—encoding 15-hydroxyprostaglandin dehydrogenase and solute carrier organic anion transporter family member 2A1 (SLCO2A1), respectively, have been identified (Diggle et al., 2012; Uppal et al., 2008; Zhang et al., 2012). Prostaglandin E 2 (PGE 2) is synthesized by cyclooxygenase, metabolized to stable prostaglandin E-major urinary metabolite (PGE-MUM), and finally excreted in the urine as PGE-MUM (Hamberg et al., 1971). PGE 2 imported by SLCO2A1 is rapidly oxidized by cytoplasmic 15-hydroxyprostaglandin dehydrogenase. Dysfunction of either of these genes is speculated to cause increased levels of PGE 2 (Sasaki et al., 2012). Two pioneer groups suggested that affected individuals having SLCO2A1 mutations have elevated urinary PGE 2; contrary to HPGD-deficient patients, they also excrete considerable quantities of the PGE 2 metabolite, PGE-M (Diggle et al., 2012; Zhang et al., 2012).