进行性假性类风湿性发育不良症的临床诊断及WISP3基因突变分析  

Clinical diagnosis and WISP3 gene mutation analysis for progressive pseudorheumatoid dysplasia

作　　者：叶军[1] 张惠文[1] 王彤[1] 曹兰芳[2] 邱文娟[1] 韩连书[1] 张雅芬[1] 顾学范[1] 

机构地区：[1]上海交通大学医学院附属新华医院上海市儿科医学研究所内分泌遗传代谢病室,200092 [2]上海交通大学医学院附属仁济医院儿科

出　　处：《中华儿科杂志》2010年第3期194-198,共5页Chinese Journal of Pediatrics

基　　金：国家高技术研究发展计划（863计划）资助项目（2007AA022447）;“十一五”国家科技支撑计划资助项目（2006BA105A05,2006BA105A07）;上海交通大学医学院科技基金资助项目（2009XJ21050）

摘　　要：目的从临床及影像学角度识别进行性假性类风湿性发育不良症（PPD）；了解PPD的基因突变类型。方法3例表现为关节疼痛、肿胀及运动障碍的患儿（9～16岁）纳入本研究。根据临床表现、骨骼影像学及实验室检查进行PPD的诊断；采用PCR及直接测序法对PPD家系进行WISP3基因突变分析。结果3例患儿符合PPD的临床诊断：表现为非炎性的多关节（包括指趾关节）膨大，影像学表现为扁平椎、椎体前缘呈鸟嘴或子弹头样改变、股骨头及外周大小关节骨骺（干骺端）扩大等，血沉、C反应蛋白、类风湿因子等实验室指标正常；3例患儿中发现了3种未见报道的WISP3基因突变，突变类型分别为巳624—625insA／c．729_735delGAGAAAA、c_624—625insA／c．866—867insA及c．866_867insA／c．866_867insA，均为插入或缺失突变，突变位于外显子4及外显子5，各占50％（3／6）。结论PPD临床特点是进行性、非炎性的多关节（包括指趾关节）膨大及运动障碍，类风湿因子等实验室指标正常；全身骨骼（包括脊柱）的影像学检查对诊断十分重要，主要特征为扁平椎、关节骨骺（干骺端）扩大及关节腔狭窄。发现了3种WISP3基因新变异。Objective Progressive pseudorheumatoid dysplasia （PPD） （MIM#208230） is a rare autosomal recessive disease of cartilage homeostasis characterized by axial and peripheral skeletal dysplasia. Analysis of WISP3 （Wntl-inducible signaling pathway protein 3, MIM#603400） gene mutation can confirm the clinical and radiographic diagnosis for PPD. This study aimed to recognize PPD based on clinical manifestations and imaging characteristics of bones, and to investigate the mutations of WISP3 gene in three patients with PPD. Method Three male patients （9-16 years old） from three unrelated Chinese families, who presented with joint pain, swelling, deformities and motion limitation, were referred to this study. PPD was diagnosed on the basis of the clinical manifestations, imaging characteristics of bones and laboratory evaluation. All five exons and their exon/intron boundaries of the WISP3 gene were amplified by polymerase chain reaction （PCR） from the peripheral blood I）NA of three PPD family members, and mutation analysis was performed by bidirectional DNA sequencing. Result （ 1 ） Three patients were diagnosed as PPD by characteristic evidences： all patients presented with non-inflammatory multiple joints swelling and stiffness including joints in hand and feet as they age. Radiographs showed platyspondyly, ovoid or wedged anterior end-plate of vertebral bodies, coxa vara, widened epiphyses or metaphyses including capital femoral, metacarpophalangea, interphalangeal joints and metatarsals. Normal laboratory values were found for the erythrocyte sedimentation rate and C-reactive protein, rheumatoid factors, antinuclear antibodies etc. （2）The three different mutations of WISP3 gene were identified in three patients with PPD, including two small insert mutations （ c. 624 _ 625insA, c. 866 _ 867insA ）, one was deletion mutation （ c. 729 _ 735delGAGAAAA）. The types of mutation of two alleles in three patients were c. 624_625insA/c. 729_735delGAGAAAA, c. 624_625insA/c. 866_867insA and c. 8

关 键 词：骨软骨发育不良 突变 WISP3基因 

分 类 号：R593.2[医药卫生—内科学]