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.
