Li Na, Ma Yuhang, Jiang Yun, You Li, Huang Yunhong, Peng Yongde, Ding Xiaoying, Zhao Li
Department of Endocrinology and Metabolism, Shanghai General Hospital, Shanghai Jiao Tong University, 100 Haining Road, Shanghai 200080, China.
International Medical Care Center, Shanghai General Hospital, Shanghai Jiao Tong University, 100 Haining Road, Shanghai 200080, China.
Int J Endocrinol. 2020 Dec 3;2020:6698878. doi: 10.1155/2020/6698878. eCollection 2020.
Primary hypertrophic osteoarthropathy (PHO) is a rare, autosomal, recessive genetic disease characterized by digital clubbing, periostosis, and pachydermia. The underlying cause for the pathogenesis of this disease is a defect in prostaglandin E2 (PGE2) degradation, caused by mutations in HPGD or SLCO2A1. In this study, we describe the clinical characteristics, SLCO2A1 mutations, and bone metabolic markers of a PHO pedigree from a Chinese consanguineous twin family.
Whole blood and urine samples were collected from all the family members. All the exons and exon-intron boundaries of the HPGD and SLCO2A1 genes were amplified using polymerase chain reaction (PCR) and sequenced. The biomarkers of mineral and bone metabolism, including calcium, phosphorus, parathyroid hormone (PTH), 25-hydroxyvitamin D (25(OH)D), bone Gla-protein (BGP), C-terminal telopeptide of type I collagen (-CTX), and urinary calcium/creatinine ratio (Uca/Ucr) were detected.
A homozygous (nonsense) mutation in the gene (c.1807C >T/p.R603 ) was detected in the proband. Five heterozygous carriers were also identified among his relatives, including his twin brother. The serum BGP (225.5 ng/ml), -CTX (4112 pg/ml), and Uca/Ucr (0.63) levels were significantly elevated, while the 25(OH)D (37.1 nmol/L) level was reduced in the proband. The proband's twin brother displayed increased levels of -CTX (901 pg/ml) and insufficiency of 25(OH)D (67.29 nmol/L), while the other heterozygous carriers only displayed 25(OH)D insufficiency.
The patients with PHO displayed an active state of bone reconstruction. There may be a lack of vitamin D, accompanied by an increase in BGP and -CTX levels. Heterozygous mutations of might lead to mild PHO.
原发性肥厚性骨关节病（PHO）是一种罕见的常染色体隐性遗传病，其特征为杵状指、骨膜增生和皮肤增厚。该疾病发病机制的根本原因是由HPGD或SLCO2A1基因突变导致的前列腺素E2（PGE2）降解缺陷。在本研究中，我们描述了一个来自中国近亲双胞胎家族的PHO家系的临床特征、SLCO2A1突变及骨代谢标志物。
采集所有家庭成员的全血和尿液样本。使用聚合酶链反应（PCR）扩增HPGD和SLCO2A1基因的所有外显子及外显子 - 内含子边界并进行测序。检测矿物质和骨代谢的生物标志物，包括钙、磷、甲状旁腺激素（PTH）、25 - 羟基维生素D（25(OH)D）、骨钙素（BGP）、I型胶原C末端肽（-CTX）以及尿钙/肌酐比值（Uca/Ucr）。
在先证者中检测到基因（c.1807C>T/p.R603 ）的纯合（无义）突变。在其亲属中还鉴定出5名杂合携带者，包括他的双胞胎兄弟。先证者的血清BGP（225.5 ng/ml）、-CTX（4112 pg/ml）和Uca/Ucr（0.63）水平显著升高，而25(OH)D（37.1 nmol/L）水平降低。先证者的双胞胎兄弟显示-CTX水平升高（901 pg/ml）和25(OH)D不足（67.29 nmol/L），而其他杂合携带者仅表现为25(OH)D不足。
PHO患者表现出骨重建的活跃状态。可能存在维生素D缺乏，同时伴有BGP和-CTX水平升高。 的杂合突变可能导致轻度PHO。
