Progressive pseudorheumatoid dysplasia(PPD,MIM 603400)is a rare autosomal recessive skeletal disorder that profoundly impairs joint function and diminishes quality of life.It is characterized by disproportionate short...Progressive pseudorheumatoid dysplasia(PPD,MIM 603400)is a rare autosomal recessive skeletal disorder that profoundly impairs joint function and diminishes quality of life.It is characterized by disproportionate short stature,extensive cartilage damage,and progressive joint enlargement symptoms typically including joint pain,stiffness,and swelling,initially affecting the interphalangeal joints before progressively involving larger joints and the spine.展开更多
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 aim...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.展开更多
基金supported by the Beijing Natural Science Foundation(China)(No.7244286)the Beijing Municipal Health Commission(China)(No.BJRITO-RDP-2025)the Beijing Natural Science Foundation-Haidian Original Innovation Joint Fund(China)(No.L222089).
文摘Progressive pseudorheumatoid dysplasia(PPD,MIM 603400)is a rare autosomal recessive skeletal disorder that profoundly impairs joint function and diminishes quality of life.It is characterized by disproportionate short stature,extensive cartilage damage,and progressive joint enlargement symptoms typically including joint pain,stiffness,and swelling,initially affecting the interphalangeal joints before progressively involving larger joints and the spine.
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).
文摘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.
文摘进行性假性类风湿发育不良(progressive pseudorheumatoid dysplasia,PPRD)是一种常染色体隐性遗传的骨发育不良性疾病,由Wnt-1诱导信号通路蛋白3(Wnt1-inducible signaling protein 3,WISP3)也称细胞通信网络因子6(cellular communication network factor 6,CCN6)基因突变引起,主要累及关节软骨组织,导致持续的软骨退化和损伤[1]。PPRD发病率低,以非炎症性多关节病为主要特征,引起脊柱和髋关节特征性骨骼异常,但无关节破坏。
