原发性肥大性骨关节病并SLCO2A1基因突变2例  

Two cases of primary hypertrophic osteoarthropathy with SLCO2A1 gene mutations

作　　者：金萍[1] 张勤[1] 何红晖[1] 朱伟豪 龙晓丹 莫朝晖[1] JIN Ping;ZHANG Qin;HE Honghui;ZHU Weihao;LONG Xiaodan;MO Zhaohui(Department of Endorcrinology, Third Xiangya Hospital, Central South University, Changsha 410013, China)

机构地区：[1]中南大学湘雅三医院内分泌科,长沙410013

出　　处：《中南大学学报（医学版）》2018年第1期100-105,共6页Journal of Central South University ：Medical Science

基　　金：国家自然科学基金(81670730;81100583);湖南省自然科学基金(2016JJ4103)~~

摘　　要：收集中南大学湘雅三医院内分泌科诊断的2例原发性肥大性骨关节病(primary hypertrophic osteoarthropathy,PHO)患者的临床资料,提取全部患者及其家族成员外周血进行基因组DNA抽提,应用PCR扩增15-羟基前列腺素脱氢酶(hydroxyprostaglandin dehydrogenase,HPGD)及SLCO2A1致病基因全部外显子、外显子和内含子交界区。PCR产物进行直接测序,并利用在线数据库Poly Phen-2及SIFT对发现的突变致病性进行预测。通过基因测序,发现该2例患者的SLCO2A1基因分别存在c.1106G>A(p.G369D)纯合子突变和c.611C>T(p.S204L)纯合子突变,均未检出HPGD基因突变。经SIFT和Poly Phen2生物信息学工具预测得出SLCO2A1基因这两个突变为致病性错义突变,证实SLCO2A1基因突变在PHO发病机制中的作用。对PHO患者进行SLCO2A1基因检测不仅有助于明确病因,也有利于产前诊断及遗传咨询。Two patients with primary hypertrophic osteoarthropathy （PHO） and their available healthy family members were studied. All exons of the SLCO2A1 and HPGD gene and adjacent exon- intron sequences were amplified by PCR and subsequently sequenced. To assess the damaging effects of missense mutations in silico, the online database, PolyPhen-2 and SIFT were used. We identified two homozygous mutations in SLCO2A1 gene： one was c. 1106G〉A （p.G369D） in exon 9, the other was c.611C〉T （p.S204L） in exon 4. No HPGD mutation was found in the affected individuals. The two mutation were predicted in silico by the bioinformatic tools. Our study further supports the role of mutations in the SLCO2A1 gene in the pathogenesis of PHO. Identification of the genotype in PHO may not only help the clinical diagnosis of PHO but also help the interpretation of genetic information for prenatal diagnosis and genetic counseling.

关 键 词：原发性肥大性骨关节病 厚皮性骨膜增生症 SLCO2A1基因 突变 

分 类 号：R684.1[医药卫生—骨科学]