caa a22 4500 605520720 CHVBK 20210128100736.0 cr unu---uuuuu 210128e20151001xx s 000 0 eng 10.1007/s00223-015-0024-3 doi (NATIONALLICENCE)springer-10.1007/s00223-015-0024-3 A Common Mutation and a Novel Mutation in the HPGD Gene in Nine Patients with Primary Hypertrophic Osteoarthropathy [Elektronische Daten] [Lu Yuan, Ling Chen, Ruo-xi Liao, Yuan-yuan Lin, Yan Jiang, Ou Wang, Mei Li, Xiao-Ping Xing, Qian-Qian Pang, Ruizhi Jiajue, Wei-bo Xia] 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. Springer Science+Business Media New York, 2015 Primary hypertrophic osteoarthropathy nationallicence Prostaglandin E2 nationallicence Prostaglandin metabolite nationallicence HPGD gene nationallicence Yuan Lu Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Shuaifuyuan No. 1, Dongcheng District, 100730, Beijing, China aut Chen Ling Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Shuaifuyuan No. 1, Dongcheng District, 100730, Beijing, China aut Liao Ruo-xi Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Shuaifuyuan No. 1, Dongcheng District, 100730, Beijing, China aut Lin Yuan-yuan Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Shuaifuyuan No. 1, Dongcheng District, 100730, Beijing, China aut Jiang Yan Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Shuaifuyuan No. 1, Dongcheng District, 100730, Beijing, China aut Wang Ou Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Shuaifuyuan No. 1, Dongcheng District, 100730, Beijing, China aut Li Mei Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Shuaifuyuan No. 1, Dongcheng District, 100730, Beijing, China aut Xing Xiao-Ping Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Shuaifuyuan No. 1, Dongcheng District, 100730, Beijing, China aut Pang Qian-Qian Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Shuaifuyuan No. 1, Dongcheng District, 100730, Beijing, China aut Jiajue Ruizhi Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Shuaifuyuan No. 1, Dongcheng District, 100730, Beijing, China aut Xia Wei-bo Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Shuaifuyuan No. 1, Dongcheng District, 100730, Beijing, China aut Calcified Tissue International Springer US; http://www.springer-ny.com 97/4(2015-10-01), 336-342 0171-967X 97:4<336 2015 97 223 https://doi.org/10.1007/s00223-015-0024-3 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00223-015-0024-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Yuan Lu Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Shuaifuyuan No. 1, Dongcheng District, 100730, Beijing, China aut NATIONALLICENCE 700 1- Chen Ling Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Shuaifuyuan No. 1, Dongcheng District, 100730, Beijing, China aut NATIONALLICENCE 700 1- Liao Ruo-xi Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Shuaifuyuan No. 1, Dongcheng District, 100730, Beijing, China aut NATIONALLICENCE 700 1- Lin Yuan-yuan Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Shuaifuyuan No. 1, Dongcheng District, 100730, Beijing, China aut NATIONALLICENCE 700 1- Jiang Yan Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Shuaifuyuan No. 1, Dongcheng District, 100730, Beijing, China aut NATIONALLICENCE 700 1- Wang Ou Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Shuaifuyuan No. 1, Dongcheng District, 100730, Beijing, China aut NATIONALLICENCE 700 1- Li Mei Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Shuaifuyuan No. 1, Dongcheng District, 100730, Beijing, China aut NATIONALLICENCE 700 1- Xing Xiao-Ping Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Shuaifuyuan No. 1, Dongcheng District, 100730, Beijing, China aut NATIONALLICENCE 700 1- Pang Qian-Qian Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Shuaifuyuan No. 1, Dongcheng District, 100730, Beijing, China aut NATIONALLICENCE 700 1- Jiajue Ruizhi Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Shuaifuyuan No. 1, Dongcheng District, 100730, Beijing, China aut NATIONALLICENCE 700 1- Xia Wei-bo Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Shuaifuyuan No. 1, Dongcheng District, 100730, Beijing, China aut NATIONALLICENCE 773 0- Calcified Tissue International Springer US; http://www.springer-ny.com 97/4(2015-10-01), 336-342 0171-967X 97:4<336 2015 97 223