Abstract: Objective　To summarize the clinical manifestations，imaging examination and WISP3 gene mutation of children with progressive pseudorheumatoid dysplasia（PPD），so as to improve the clinical understanding of the disease. Methods　The clinical data and genetic results of 6 children with PPD admitted to the Department of Endocrinology，Capital Center for Children's Health，Capital Medical University from December 2017 to April 2023 were retrospectively analyzed. Results　The 6 children with PPD were diagnosed at 5.4-12.8 years old，2 males and 4 females，and they visited the hospital for short stature，joint enlargement/pain，and abnormal walking posture. Four cases were with short stature and 2 cases were with slightly short stature. Blood calcium，blood phosphorus，alkaline phosphatase and 25 （OH）D levels and inflammatory indicators were normal in all children. Imaging examination showed that the vertebrae were flat and in irregular shape，and there were scoliosis and multiple swollen joints. All patients underwent whole exome sequencing（WES）. WISP3 gene mutation was detected in all patients，with homozygous mutation in 2 cases and complex heterozygous mutation in 4 cases.Among the 7 alleles，there were 3 missense mutations，2 frameshift mutation，1 shear mutation and 1 termination mutation，among which c.271delC（p.L91Sfs*14）was an unreported new mutation. Conclusion　The main clinical manifestations of PPD in children are short stature or slightly short stature，symmetric enlargement and pain of multiple joints. The results of genetic testing provide evidence for confirming diagnosis and genetic counseling for the family.The discovery of the new variant has enriched the spectrum of WISP3 gene variations.

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摘要： 目的　对进行性假性类风湿性发育不良症（progressive pseudorheumatoid dysplasia，PPD）患儿的临床表现、影像学检查及WISP3基因变异情况进行总结，进一步提高临床对该病的认识。方法　回顾性分析2017年12月至2023年4月首都医科大学附属首都儿童医学中心内分泌科收治的6例PPD患儿的临床资料及基因结果。结果　6例PPD患儿的诊断年龄5.4~12.8岁，男2例，女4例，因身材矮小、关节肿大/疼痛、行走姿势异常就诊。4例患儿身材矮小，2例身材偏矮。所有患儿血钙、血磷、碱性磷酸酶及维生素D水平均正常，炎症指标无增高。影像学检查显示椎体扁平、形态不规则，脊柱侧弯，多关节膨大。所有患儿均进行了全外显子测序（WES）检测，均检测出WISP3基因变异，2例为纯合突变，4例为复合杂合突变；7个等位基因变异中3个错义变异、2个移码变异、1个剪切变异和1个终止变异，其中c.271delC（p.L91Sfs*14）为未报道的新变异。结论　儿童PPD临床以身材矮小或偏矮、多关节对称性膨大与疼痛为主要临床表现。基因检测结果为明确诊断、家系的遗传咨询提供了依据。新变异的发现丰富了WISP3基因变异谱。

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