title: A Common Mutation and a Novel Mutation in the HPGD Gene in Nine Patients with Primary Hypertrophic Osteoarthropathy.
abstract: 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.
authors.affiliation: 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, Beijing, 100730, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Yuan
authors.affiliation: 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, Beijing, 100730, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
authors.affiliation: 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, Beijing, 100730, China.
authors.forename: Ruo-xi
authors.initials: RX
authors.lastname: Liao
authors.affiliation: 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, Beijing, 100730, China.|Department of Endocrinology, The First Affiliated Hospital of Shanxi Medical University, Taiyuan, 030001, China.
authors.forename: Yuan-yuan
authors.initials: YY
authors.lastname: Lin
authors.affiliation: 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, Beijing, 100730, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: 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, Beijing, 100730, China.
authors.forename: Ou
authors.initials: O
authors.lastname: Wang
authors.affiliation: 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, Beijing, 100730, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Li
authors.affiliation: 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, Beijing, 100730, China.
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Xing
authors.affiliation: 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, Beijing, 100730, China.|Department of Endocrinology, The First Affiliated Hospital of Shanxi Medical University, Taiyuan, 030001, China.
authors.forename: Qian-Qian
authors.initials: QQ
authors.lastname: Pang
authors.affiliation: 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, Beijing, 100730, China.
authors.forename: Ruizhi
authors.initials: R
authors.lastname: Jiajue
authors.affiliation: 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, Beijing, 100730, China. xiaweibo@medmail.com.cn.
authors.forename: Wei-bo
authors.initials: WB
authors.lastname: Xia
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D006911:Hydroxyprostaglandin Dehydrogenases / Q000235:genetics*; D008297:Male; D009154:Mutation; D010004:Osteoarthropathy, Primary Hypertrophic / Q000235:genetics*; D055815:Young Adult
chemical_list: D006911:Hydroxyprostaglandin Dehydrogenases; C035859:15-hydroxyprostaglandin dehydrogenase
keywords: HPGD gene; Primary hypertrophic osteoarthropathy; Prostaglandin E2; Prostaglandin metabolite