Clinical and biochemical characteristics of 12 Chinese primary hypertrophic osteoarthropathy patients with HPGD mutations.
Clinical and biochemical characteristics of 12 Chinese primary hypertrophic osteoarthropathy patients with HPGD mutations.
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12例HPGD突变的中国原发性肥厚性骨关节病患者的临床及生化特征
DOI：
10.7150/ijbs.71261
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发表时间：
2022
影响因子：
9.2
通讯作者：
Zhang, Zhenlin
中科院分区：
文献类型：
--
作者：
Lu, Qi;Xu, Yang;Li, Shanshan;Zhang, Zeng;Sheng, Jiagen;Zhang, Zhenlin
原发性肥大性骨关节病是一种罕见的遗传性疾病，主要累及骨骼和皮肤。已知参与前列腺素降解的两个基因负责PHO：HPGD和SLCO 2A 1。HPGD基因突变可引起PHO常染色体隐性遗传1型（PHOAR 1）。本研究旨在分析12例中国人PHOAR 1患者的临床、生化特征及HPGD基因突变情况。来自11个家庭的12名PHOAR 1患者，包括11名男性和1名女性，入组本研究。数字杵状和骨膜增生出来是最常见的特征，这总是发生在儿童早期。我们进行了HPGD基因分析并鉴定了六种新的（c.1A>G、c.34G>T、c.317T>A、c.475G>T、c.548C>T和c.421+1G>T）和一种已知的（c.310_311delCT）HPGD突变。11例患者均发现复发突变c.310_311delCT，提示其为热点突变。PHOAR 1患者被认为具有常染色体隐性遗传模式。在这里，除了9名复合杂合子患者和2名纯合子患者，我们发现了1名杂合子患者，并审查了其他研究中报道的2名杂合子患者。在生化特征方面，我们的PHOAR 1患者与健康对照组相比，尿前列腺素E2（PGE 2）水平升高（P<0.001），尿前列腺素E代谢产物（PGE-M）水平降低（P=0.04）。PGE_2/PGE-M（E/M）比值明显低于正常人（P<0.001）。这项研究提供了一个全面的描述中国PHOAR 1患者的临床表型，并扩大了疾病的基因型谱。
Primary hypertrophic osteoarthropathy (PHO) is a rare genetic disease mainly affecting the skeletal and skin. Two genes involved in prostaglandin degradation are known to be responsible for PHO: HPGD and SLCO2A1. HPGD gene mutation can cause PHO autosomal recessive 1 (PHOAR1). The purpose of the present study is to analyze the clinical and biochemical characteristics and HPGD gene mutations of 12 Chinese PHOAR1 patients. Twelve PHOAR1 patients from eleven families, including eleven males and one female, were enrolled in this study. Digital clubbing and periostosis came out to be the most common features, which always occur in the early childhood. We performed HPGD gene analysis and identified six novel (c.1A>G, c.34G>T, c.317T>A, c.475G>T, c.548C>T and c.421+1G>T) and one known (c.310_311delCT) HPGD mutations. The recurrent mutation c.310_311delCT were found in all eleven patients, suggesting it is a hotspot mutation. PHOAR1 patients are considered to have an autosomal recessive inheritance pattern. Here, in addition to nine compound heterozygous patients and two homozygous patients, we found one heterozygous patient and reviewed two heterozygous patients reported in other studies. In terms of biochemical characteristics, our PHOAR1 patients have elevated urinary prostaglandin E2 (PGE2) levels (P<0.001) and decreased urinary prostaglandin E metabolite (PGE-M) levels (P=0.04) compared with healthy controls. The patients' PGE2/PGE-M (E/M) ratio came out to be lower than normal subjects (P<0.001). This study provides a comprehensive description of the clinical phenotypes of Chinese PHOAR1 patients and expands the genotypic spectrum of the disease.
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影响因子：
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作者：
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通讯作者：
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影响因子：
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