Unique mutation spectrum of progressive pseudorheumatoid dysplasia in the Chinese population:a retrospective genotype-phenotype analysis of 105 patients  

作　　者：Wei Wang Si-Hao Gao Min Weil Lin-Qing Zhong Wei Liu Shan Jian Juan Xiao Cai-Hui Zhang Jian-Guo Zhang Xiao-Feng Zeng Wei-Bo Xia Zheng-Qing Qiu Hong-Mei Song 

机构地区：[1]Department of Pediatrics,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,No.1 Shuaifuyuan,Dongcheng,Beijing 100730,China [2]Department of Radiology,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100730,China [3]Department of Orthopedic Surgery,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100730,China [4]Department of Rheumatology and Clinical Immunology,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100730,China [5]National Clinical Research Center for Dermatologic and Immunologic Diseases(NCRC-DID),Ministry of Science and Technology,Beijing 100730,China [6]State Key Laboratory of Complex Severe and Rare Diseases,Peking Union Medical College Hospital(PUMCH),Beijing 100730,China [7]Key Laboratory of Rheumatology and Clinical Immunology,Ministry of Education,Beijing 100730,China [8]Department of Endocrinology,National Health Commission Key Laboratory of Endocrinology,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100730,China

出　　处：《World Journal of Pediatrics》2023年第7期674-686,共13页世界儿科杂志（英文版）

基　　金：the CAMS Innovation Fund for Medical Sciences(CIFMS 2021-I2M-1-003);the National Key R&DProgramof China(2021YFC2702001,2016YFC0901500);National High Level Hospital Clinical Research Funding(2022-PUMCH-B-079).

摘　　要：Background Progressive pseudorheumatoid dysplasia(PPRD)is a rare genetic disease with autosomal recessive inherit-ance.There was a lack of genotype-phenotype correlation data from the Chinese population.This study aimed to identify the genotype and phenotype characteristics of Chinese PPRD patients and to conduct a genotype-phenotype analysis of Chinese PPRD patients.Methods Genetic analysis was performed for suspected PPRD patients from Peking Union Medical College Hospital.Medi-cal records were collected from the electronic medical record system and patient-held portable health records.Published Chinese PPRD cases were gathered from both international and Chinese local databases.We collected demographic infor-mation,genetic variants,clinical manifestations,and imaging characteristics for further analysis.Results We included 105 Chinese PPRD patients in the current study.Thirty-three variants,including nine novels and five hotspot variants,were identified,with 26/33(79%)variants exclusively seen in the Chinese population.Chinese PPRD patients share a phenotype similar to that in international reports.Joint involvement may progress with age(R2=0.2541).Long bone shortening and severe deformities occur in three patients with biallelic null variants,of which at least one vari-ant is located in exon 2.Among hotspot variants,c.624dupA(p.C209Mfs*21)were associated with later onset and more involved joints.Elbow joints were more likely to be affected in patients carrying c.624dupA(p.C209Mfs*21)and c.866dupA(p.S209Efs*13).Shoulder joints are more likely to be involved in patients with biallelic null variants(P=0.027).Conclusions Chinese PPRD patients share a unique mutation spectrum.Among the five hotspot variants,c.624dupA is associated with later onset of disease,more extensive joint involvement,and a tendency to affect elbow joints.Biallelic null variants with at least one variant in exon 2 could be a likely cause of long bone shortening and severe deformities.

关 键 词：CCN6 GENETICS MUTATIONS Progressive pseudorheumatoid dysplasia WISP3 

分 类 号：R725[医药卫生—儿科]