A Common Mutation and a Novel Mutation in the HPGD Gene in Nine Patients with Primary Hypertrophic Osteoarthropathy
A Common Mutation and a Novel Mutation in the HPGD Gene in Nine Patients with Primary Hypertrophic Osteoarthropathy
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9例原发性肥厚性骨关节病患者HPGD基因的常见突变和新突变
DOI：
10.1007/s00223-015-0024-3
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发表时间：
2015-10-01
影响因子：
4.2
通讯作者：
Xia, Wei-bo
中科院分区：
文献类型：
--
作者：
Yuan, Lu;Chen, Ling;Xia, Wei-bo
原发性肥大性骨关节病（PHO）是一种遗传性骨病，其特征是指杵状畸形、骨膜增生和厚皮症。发现编码15-前列腺素脱氢酶的HPGD基因和编码一种类型的前列腺素转运蛋白的SLCO 2A 1负责PHO。任何一个基因的突变都会导致前列腺素E2（PGE 2）水平升高，这可能有助于症状的发生。本研究的目的是分析HPGD基因和9例PHO患者的临床特征。9例患者（8例男性和1例女性），包括2例兄弟姐妹和7例散发病例，入组本研究。总结临床特征，并收集血液和尿液样本。采用桑格法测定HPGD基因序列，检测突变。测量每例患者的尿PGE 2和前列腺素代谢物（PGE-M）水平，并与健康对照组进行比较。在所有患者中鉴定出复发性c.310_311delCT突变，其中6例为纯合子，2例为杂合子，1例为复合杂合子，具有该突变和新的杂合错义突变c.488G>A（p.R163H）。所有患者尿中PGE 2水平均明显高于正常值，沿着PGE-M水平降低。总之，9例PHO患者的特征在于典型的临床表现，包括手指杵状畸形，骨膜增生和厚皮症。HPGD基因中的一个常见突变和一个新突变被确定为导致该疾病的原因，c.310_311delCT突变可能是亚洲PHO患者的热点突变位点。
Primary hypertrophic osteoarthropathy (PHO) is a hereditary bone disease characterized by digital clubbing, periostosis, and pachydermia. The HPGD gene encoding 15-prostaglandin dehydrogenase and SLCO2A1 encoding one type of prostaglandin transporter were found to be responsible for PHO. Mutations of either gene would lead to increased level of prostaglandin E2 (PGE2), which might contribute to the constellation of the symptoms. The aim of the study was to analyze the HPGD gene and the clinical characteristics in nine patients with the diagnosis of PHO. Nine patients, (eight males and one female) including two siblings and seven sporadic cases, were enrolled in the study. Clinical features were summarized, and blood and urine samples were collected. Sanger method was used to sequence the HPGD gene to detect mutations. Urinary PGE2 and prostaglandin metabolite (PGE-M) levels for each patient were measured and compared to the healthy controls. A recurrent c.310_311delCT mutation was identified in all patients, of which six were homozygous, two were heterozygous, and one was compound heterozygous with this mutation and a novel heterozygous missense mutation c.488G>A (p.R163H). The levels of PGE2 in urine were much higher than normal in all patients, along with lower PGE-M levels. In conclusion, nine PHO patients were characterized by typical clinical manifestations including digital clubbing, periostosis, and pachydermia. A common mutation and a novel mutation in HPGD gene were identified to be responsible for the disease, and c.310_311delCT mutation is likely to be a hot-spot mutation site for Asian PHO patients.