进行性假性类风湿性发育不良症5例临床和新型WISP3基因突变分析  

Clinical diagnosis of progressive pseudorheumatoid dysplasia in 5 cases and a report of novel WISP3 gene mutation

作　　者：茅幼英[1] 周纬[1] 金燕樑[1] 王剑[2] 沈永年[3] 周云芳[3] 顾龙君[3] 应大明[3] 殷蕾[1,3] MAO Youying;ZHOU Wei;JIN Yanliang;WANG Jian;SHEN Yongnian;ZHOU Yunfang;GU Longjun;YING Daming;YIN Lei(Nephrology and Rheumatology Department,Shanghai Children’s Medical Center,Shanghai Jiao Tong University School of Medicine,Shanghai 200127,China;Diagnosis and Treatment Center of Rare Diseases,Shanghai Children’s Medical Center,Shanghai Jiao Tong University School of Medicine,Shanghai 200127,China;Department of Medical Genetics and Molecular Diagnostic Laboratory,Shanghai Children’s Medical Center,Shanghai Jiao Tong University School of Medicine,Shanghai 200127,China)

机构地区：[1]上海交通大学医学院附属上海儿童医学中心肾脏风湿科,上海200127 [2]上海交通大学医学院附属上海儿童医学中心遗传代谢科,上海200127 [3]上海交通大学医学院附属上海儿童医学中心罕见病诊治中心,上海200127

出　　处：《临床儿科杂志》2018年第7期537-540,共4页Journal of Clinical Pediatrics

摘　　要：目的探讨进行性假性类风湿性发育不良症(PPRD)的早期诊断。方法回顾5例确诊PPRD患儿的临床资料以及基因检测结果。结果 5例患儿中男1例、女4例,发病年龄3～5岁,确诊时年龄8～12岁。均存在手指指间关节增大,1例走路时步态异常,4例存在跛行,病程中均有关节疼痛和活动受限。5例患儿炎症指标均正常。X线检查示5例患儿均出现手指关节干骺端膨大,骨密度降低;脊柱椎体前端变尖变扁,部分椎间隙变窄,1例椎体呈子弹头样改变。5例患儿均存在WISP3基因突变,1例为c.397_404del CAAGTGTT(纯合);2例为NM_19829.1:c.700T>C,p.Trp234Arg(母亲杂合),NM_19829.1:c.1054T>C,p.Ser352Pro(父亲杂合)复合杂合突变;另2例为c.589+2T>C(母亲杂合),c.667T>G,p.Cys223Gly(父亲杂合)复合杂合突变。除c.667T>G和c.589+2T>C外,余3个为未报道的新突变位点。结论 PPRD的临床特点为多关节的非炎症性膨大和运动障碍;放射学特征性改变为关节骨骺端增大、发育异常和椎体变尖变扁;在临床特点和放射学典型改变基础上,结合WISP3基因检测可以明确诊断。该研究发现了3种新的WISP3基因突变位点。Objective To explore the early diagnosis of progressive pseudorheumatoid dysplasia(PPRD).Method The clinical data and gene detection results of PPRD in 5 children were reviewed.Results In 5 children(1 boy,4 girls),the age at onset was 3~5 years and at the time of diagnosis was 8~12 years.All of them suffered from interphalangeal joint enlargement.One had gait abnormality and 4 had claudication.All patients had joint pain and limited activity during the course of the disease.However,the inflammatory markers were all normal in 5 patients.The X-ray examination showed the metaphysis of the finger joint was swollen and the bone density was reduced.The anterior segment of the spine became flattened and the part of the intervertebral space was narrowed.In one case,the vertebral body presented a warhead-like change.All of the five cases had WISP3 gene mutation.One case had homozygous mutation of c.397_404del CAAGTGTT,2 cases had complex heterozygous mutations(NM_19829.1:c.700T>C,p.Trp234Arg from mother;NM_19829.1:c.1054T>C,p.Ser352Pro from father),and another 2 cases had complex heterozygosity mutations(c.589+2T>C from mother,c.667T>G;p.Cys223Gly from father).Except for c.667T>G and c.589+2T>C,the remaining 3 were unreported new mutations.Conclusion The clinical features of PPRD are non-inflammatory expansion of multiple joints and dyskinesia.The radiological features included enlargement of articular epiphysis,abnormal development and progressive platyspondyly.Based on clinical characteristics and typical changes of radiology,combined with WISP3 gene detection,definite diagnosis can be made.The study also identified 3 new mutations in the WISP3 gene.

关 键 词：进行性假性类风湿性发育不良症 WISP3基因 儿童 

分 类 号：R725.9[医药卫生—儿科]