Background Pseudoachondroplasia （PSACH） is an autosomal-dominant osteochondrodysplasia due to mutations in the gene encoding cartilage oligomeric matrix protein （COMP）.Clinical diagnosis of PSACH is based primaril...Background Pseudoachondroplasia （PSACH） is an autosomal-dominant osteochondrodysplasia due to mutations in the gene encoding cartilage oligomeric matrix protein （COMP）.Clinical diagnosis of PSACH is based primarily on family history, physical examination, and radiographic evaluation.There is evidence that decreased serum COMP concentration may serve as a diagnostic marker in PSACH.Here, we investigated the role of this gene and the serum COMP concentration in Chinese patients with PSACH.Methods A family with three patients and a sporadic case were recruited.Genomic and phenotypic data were recorded.The diagnosis of PSACH was made on the base of clinical evaluation.The genomic DNA was extracted from peripheral blood leukocytes.The 8-19 exons and flanking intron-exon boundary sequences of COMP were amplified by polymerase chain reaction （PCR） and screened for mutation by direct DNA sequencing.Serum COMP concentrations of 4 patients and age-compatible control group of 20 unrelated healthy subjects were analyzed on the basis of an ELISA Kit for human cartilage oligomeric matrix protein.Results A deletion （c.1447-1455del） was identified in exon 13 in the sporadic case.The mean serum COMP concentrations of four patients （3.12±2.28） were significantly lower than those of control group （10.86±2.21, P 〈0.05）.There was no overlap in the distribution of serum COMP concentration between PSACH patients and controls.Conclusions Mutations in COMP gene are responsible for the PSACH.Serum COMP concentration may be suggested as an additional diagnostic marker to aid clinical findings in suspected cases of PSACH.展开更多
Pseudoachondroplasia(PSACH)is a relatively common skeletal dysplasia characterized by disproportionate short stature,joint laxity,early-onset osteoarthrosis,and dysplasia of the spine,epiphysis,and metaphysis.It is kn...Pseudoachondroplasia(PSACH)is a relatively common skeletal dysplasia characterized by disproportionate short stature,joint laxity,early-onset osteoarthrosis,and dysplasia of the spine,epiphysis,and metaphysis.It is known as an autosomal dominant disease which results exclusively from mutations in the gene for Cartilage Oligomeric Matrix Protein(COMP).We have identified a five year old Chinese boy who was diagnosed as pseudoachondroplasia according to clinical manifestations and X-ray symptoms.His mother seems like another effected individual because of the apparent short stature.Genomic DNA was extracted from peripheral blood lymphocytes.DNA sequencing analysis of the COMP gene revealed a heterozygous mutation(c.1219 T>C,p.Cys407Arg)in the patient.His mother was also affected with the same genetic change.Mutations in COMP gene is proved to change the Cartilage Oligomeric Matrix Protein.This missense mutation(c.1219 T>C)has not been reported before and it is not belongs to polymorphism sites.Our results extend the spectrum of mutations in COMP gene leading to pseudoachondroplasia.展开更多
文摘Background Pseudoachondroplasia （PSACH） is an autosomal-dominant osteochondrodysplasia due to mutations in the gene encoding cartilage oligomeric matrix protein （COMP）.Clinical diagnosis of PSACH is based primarily on family history, physical examination, and radiographic evaluation.There is evidence that decreased serum COMP concentration may serve as a diagnostic marker in PSACH.Here, we investigated the role of this gene and the serum COMP concentration in Chinese patients with PSACH.Methods A family with three patients and a sporadic case were recruited.Genomic and phenotypic data were recorded.The diagnosis of PSACH was made on the base of clinical evaluation.The genomic DNA was extracted from peripheral blood leukocytes.The 8-19 exons and flanking intron-exon boundary sequences of COMP were amplified by polymerase chain reaction （PCR） and screened for mutation by direct DNA sequencing.Serum COMP concentrations of 4 patients and age-compatible control group of 20 unrelated healthy subjects were analyzed on the basis of an ELISA Kit for human cartilage oligomeric matrix protein.Results A deletion （c.1447-1455del） was identified in exon 13 in the sporadic case.The mean serum COMP concentrations of four patients （3.12±2.28） were significantly lower than those of control group （10.86±2.21, P 〈0.05）.There was no overlap in the distribution of serum COMP concentration between PSACH patients and controls.Conclusions Mutations in COMP gene are responsible for the PSACH.Serum COMP concentration may be suggested as an additional diagnostic marker to aid clinical findings in suspected cases of PSACH.
基金We thank the members for the participation.This study was supported by the grants from the Key Program of Chongqing Health and Family Planning Commission(NO.[2013]39:2013-1-029).
文摘Pseudoachondroplasia(PSACH)is a relatively common skeletal dysplasia characterized by disproportionate short stature,joint laxity,early-onset osteoarthrosis,and dysplasia of the spine,epiphysis,and metaphysis.It is known as an autosomal dominant disease which results exclusively from mutations in the gene for Cartilage Oligomeric Matrix Protein(COMP).We have identified a five year old Chinese boy who was diagnosed as pseudoachondroplasia according to clinical manifestations and X-ray symptoms.His mother seems like another effected individual because of the apparent short stature.Genomic DNA was extracted from peripheral blood lymphocytes.DNA sequencing analysis of the COMP gene revealed a heterozygous mutation(c.1219 T>C,p.Cys407Arg)in the patient.His mother was also affected with the same genetic change.Mutations in COMP gene is proved to change the Cartilage Oligomeric Matrix Protein.This missense mutation(c.1219 T>C)has not been reported before and it is not belongs to polymorphism sites.Our results extend the spectrum of mutations in COMP gene leading to pseudoachondroplasia.
