Genetic analysis and serum level of cartilage oligomeric matrix protein in patients with pseudoachondroplasia

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Author:
LIU Feng-xia(Department of Medical Genetics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, WHO Collaborating Centre for Community Control of Hereditary Diseases, Beijing 100730, China;Department of Rheumatology Weifang People's Hospital, Weifang, Shandong 261042,China)
LI Zhi-ling(Department of Rehabilitation Therapy Weifang People's Hospital, Weifang, Shandong 261042,China)
WEI Zhen-ji(Department of Rehabilitation Therapy, Tai'an Central Hospital,Tai'an, Shandong 271000, China)
MENG yan(Department of Medical Genetics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, WHO Collaborating Centre for Community Control of Hereditary Diseases, Beijing 100730, China)
REN Cui-ai(Department of Hematology Weifang People's Hospital, Weifang, Shandong 261042,China)
ZHANG Xu-de(Department of Medical Genetics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, WHO Collaborating Centre for Community Control of Hereditary Diseases, Beijing 100730, China)
YU Meng-xue(Department of Rheumatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730, China)
HUANG Shang-zhi(Department of Medical Genetics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, WHO Collaborating Centre for Community Control of Hereditary Diseases, Beijing 100730, China)
Journal Title:
CHINESE MEDICAL JOURNAL
Issue:
Volume 123, Issue 16, 2010
DOI:
10.3760/cma.j.issn.0366-6999.2010.16.004
Key Word:
pseudoachondroplasia;cartilage oligomeric matrix protein;mutation screening;serum

Abstract: 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.

  • [1]McKeand J,Rotta J,Hecht JT.Natural history study of pseudoachondroplasia.Am J Med Genet 1996; 63:406-410.
  • [2]Hecht JT,Nelson LD,Crowder E,Wang Y,Elder FF,Harrison WR,et al.Mutations in exon 17B of cartilage oligomeric matrix protein (COMP) cause pseudoachondroplasia.Nat Genet 1995; 10:325-329.
  • [3]Briggs MD,Hoffman SM,King LM,Olsen AS,Mohrenweiser H,Leroy JG,et al.Pseudoachondroplasia and multiple epiphyseal dysplasia due to mutations in the cartilage oligomeric matrix protein gene.Nat Genet 1995; 10:330-336.
  • [4]Gellis SS,Feingold M,Hall JG.Pseudoachondroplasia(pseudoachondroplastic spondyloepiphyseal dysplasia).Am J Dis Child 1974; 128:833-834.
  • [5]Briggs MD,Chapman KL.Pseudoachondroplasia and multiple epiphyseal dysplasia:mutation review,molecular interactions,and genotype to phenotype correlations.Hum Mut 2002; 19:465-478.
  • [6]Briggs MD,Mortier GR,Cole WG,King LM,Golik SS,Bonaventure J,et al.Diverse mutations in the gene for cartilage oligomeric matrix protein in the pseudoachondroplasia-multiple epiphyseal dysplasia disease spectrum.Am J Hum Genet 1998; 62:311-319.
  • [7]Rimoin DL,Rasmussen IM,Briggs MD,Roughley PJ,Gruber HE,Warman ML,et al.A large family with features of pseudoachondroplasia and multiple epiphyseal dysplasia:exclusion of seven candidate gene loci that encode proteins of the cartilage extracellular matrix.Hum Genet 1994; 93:236-242.
  • [8]Unger S,Hecht JT.Pseudoachondroplasia and multiple epiphyseal dysplasia:New etiologic developments.Am J Med Genet 2001; 106:244-250.
  • [9]DiCesare P,Hauser N,Lehman D,Pasumarti S,Paulsson M.Cartilage oligomeric matrix protein (COMP) is an abundant component of tendon.FEBS Lett 1994; 354:237-240.
  • [10]Hecht JT,Deere M,Putnam E,ColeW,Vertel BM,Chen H,et al.Characterization of cartilage oligomeric matrix protein(COMP) in human normal and pseudoachondroplasia musculoskeletal tissues.Matrix Biol 1998; 17:269-278.
  • [11]Smith RKW,Zunino L,Webbon RM,Heinegard D.The distribution of cartilage oligomeric matrix protein (COMP) in tendon and its variation with tendon site,age,and load.Matrix Biol 1997; 16:255-271.
  • [12]Oldberg A,Antonsson P,Lindblom K,Heinegard D.COMP(cartilage oligomeric matrix protein) is structurally related to the thrombospondins.J Biol Chem 1992; 267:22346-22350.
  • [13]Deere M,Sanford T,Francomano CA,Daniels K,Hecht JT.Identification of nine novel mutations in cartilage oligomeric matrix protein in patients with pseudoachondroplasia and multiple epiphyseal dysplasia.Am J Med Genet 1999; 85:486-490.
  • [14]Mabuchi A,Momohara S,Ohashi H,Takatori Y,Haga N,Nishimura G,et al.Circulating COMP is decreased in pseudoachondroplasia and multiple epiphyseal dysplasia patients carrying COMP mutations.Am J Med Genet A 2004;129:35-38.
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