This study aimed to report the clinical characteristics and COMP gene mutation of a family with pseudoachondroplasia (PSACH), a relatively rare spinal and epiphyseal dysplasia that is inherited as an autosomal dominant trait. Clinical information on a 5-year-2-month-old PSACH child and his parents was collected and analyzed. Diagnosis was confirmed by PCR amplification and direct sequencing of all the 19 exons and their flanking sequences of COMP gene, and the mutation was further ascertained by cloning analysis of exon 10. The child presented with short and stubby fingers, bow leg, short limb dwarfism and metaphysic broadening in long bone as well as lumbar lordosis. A mutation c.1048_1116del (p.Asn350_Asp372del) in exon 10, inherited from his father who did not demonstrate any phenotypic feature of PSACH, was detected in the child. PSACH was diagnosed definitively by means of COMP mutation analysis, on the basis of the child's clinical and imaging features. The non-penetrance phenomenon of COMP mutation was described for the first time in PSACH.
Achondroplasia ; genetics ; Cartilage Oligomeric Matrix Protein ; genetics ; Child, Preschool ; Cloning, Molecular ; Humans ; Male ; Mutation

OBJECTIVE: To detect the expression of cartilage oligomeric matrix protein (COMP) in the synovial chondromatosis of the temporomandibular joint (TMJSC), and to discuss the possible interactions between COMP, transforming growth factor (TGF)-β3, TGF-β1 and bone morphogenetic protein-2 (BMP-2) in the development of this neoplastic disease. METHODS: Patients in Peking University School and Hospital of Stomatology from January 2011 to February 2020 were selected, who had complete medical records, TMJSC was verified histologically after operation. The expressions of COMP, TGF-β3, TGF-β1 and BMP-2 in the TMJSC of the temporomandibular joint were detected by immunohistochemistry and quantitative real-time PCR (RT-PCR) at the protein level and mRNA level respectively, compared with the normal synovial tissue of temporomandibular joint. The histological morphology, protein expression and distribution of TMJSC tissues were observed microscopically, and the positive staining proteins were counted and scored. SPSS 22.0 statistical software was used to analyze the expression differences between the related proteins in TMJSC tissue and the normal synovial tissue of temporomandibular joint and to compare their differences. P < 0.05 indicated that the difference was statistically significant. RESULTS: Immunohistochemical results showed that the positive expression of COMP in TMJSC tissues was mostly found in synovial tissues and chondrocytes adjacent to synovial tissues, and the difference was statistically significant, compared with the normal temporomandibular joint synovial tissues. The positive expression of COMP was significantly different between recurrent TMJSC and non-recurrent ones. The positive expressions of TGF-β3, TGF-β1 and BMP-2 were higher than the normal synovial tissue, and were also mostly found in the synovial cells and adjacent chondrocytes, which was further confirmed by Western blot. According to the RT-PCR results, the expressions of COMP, TGF-β3, TGF-β1 and BMP-2 in TMJSC were higher than those in the normal synovial tissue. CONCLUSION The expression of COMP in TMJSC of temporomandibular joint increased significantly, compared with the normal synovial tissue. There may be interactions between COMP and cytokines related to the proliferation and differentiation, like TGF-β3, TGF-β1 and BMP-2, which may play a potential role in the pathogenesis of TMJSC.
Cartilage Oligomeric Matrix Protein/genetics* ; Chondromatosis, Synovial ; Humans ; Synovial Membrane ; Temporomandibular Joint ; Transforming Growth Factor beta3

BACKGROUNDMultiple epiphysis dysplasia (MED) is a common skeletal dysplasia with a significant locus heterogeneity. In the majority of clinically defined cases, mutations have been identified in the gene encoding cartilage algometric matrix protein (COMP).

METHODSFive patients were included in the study. Linkage analysis and mutation analysis of the COMP gene were conducted in the patients and their family members.

RESULTSWe have identified a novel mutation in axon 14 of COMP gene in the family.

CONCLUSIONSThis mutation produced a severe MED phenotype with marked short stature, early onset osteoarthritis, and remarkable radiographic changes. Our results extended the range of disease-causing mutations in COMP gene and contributed more information about relationship between mutations and phenotype.

Adolescent ; Asian Continental Ancestry Group ; Cartilage Oligomeric Matrix Protein ; genetics ; Female ; Humans ; Male ; Osteochondrodysplasias ; genetics ; Pedigree ; Point Mutation ; genetics

OBJECTIVETo perform mutation analysis for a female with multiple epiphyseal dysplasia (MED) and provide pre-symptomatic and prenatal diagnosis.

METHODSMutation screening of cartilage oligomeric matrix protein (COMP) gene was carried out through targeted next-generation DNA sequencing and Sanger sequencing.

RESULTSA novel c.956 A>T resulting in substitution of Aspartic acid 319 for Valine (p.Asp319Val) has been identified in exon 9 of the COMP gene in the patient. As predicted by a SIFT software, above mutation can cause damage to the structure of COMP protein.

CONCLUSIONA novel c.956 A>T substitution mutation has been identified in a patient featuring MED.

Adult ; Base Sequence ; Cartilage Oligomeric Matrix Protein ; Exons ; Extracellular Matrix Proteins ; genetics ; Female ; Glycoproteins ; genetics ; Humans ; Matrilin Proteins ; Mutation ; Osteochondrodysplasias ; diagnosis ; genetics ; Polymorphism, Single Nucleotide ; Sequence Alignment

BACKGROUNDPseudoachondroplasia (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.

METHODSA 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.

RESULTSA 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.

CONCLUSIONSMutations 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.

Cartilage Oligomeric Matrix Protein ; Child, Preschool ; Enzyme-Linked Immunosorbent Assay ; Exons ; genetics ; Extracellular Matrix Proteins ; blood ; genetics ; Female ; Glycoproteins ; blood ; genetics ; Humans ; Male ; Matrilin Proteins ; Mutation ; Osteochondrodysplasias ; blood ; genetics ; Pedigree ; Polymerase Chain Reaction

OBJECTIVESTo investigate the association between matrilin-1 gene polymorphism and bracing effectiveness in adolescent idiopathic scoliosis girls.

METHODSIn a prospective study, AIS girls treated with standard bracing from January 2005 to December 2008 were included and followed up. All subjects of the study met the following criteria: female; skeletally immature (Risser sign grade 0 - 3); before menarche or < 1.5 years after menarche; Cobb angle 20 degrees - 40 degrees ; scoliosis caused by congenital, neuromuscular and other cause were excluded; no evidence of bone diseases, metabolic diseases or other condition known to affect bone metabolism; no history of bracing before onset; follow-up with an interval of 3 months, and total follow-up time > 2 years. Subjects met one of the following conditions was excluded: the final follow-up time < 2 years; bad compliance (ratio of the actual daily wearing time to proposed wearing time) of bracing (< 75%); change of bracing without doctor's order. Cobb angle of major curve was recorded before the bracing initiation and at the final follow-up. A progression of 6 degrees or more was considered to be a failure of bracing. The rs1149048 polymorphism in promoter of matrilin-1 gene was chosen for genotyping by PCR-RFLP method. Differences in age at initial visit, Risser sign, Cobb angle and genotype distribution were compared between brace failure and brace success groups.

RESULTSSeventy seven patients with AIS were included, with a mean age at (13.0 +/- 1.5) years and a mean Cobb angle at (30.3 +/- 11.9) degrees . After an average duration of 2.6 years follow-up, mean Cobb angle was 30.3 degrees +/- 11.9 degrees . There were 19 cases (24.7%) in bracing failure and 58 cases (75.3%) in bracing success. The initial Cobb angle was larger in bracing failure group compared with bracing success group (P > 0.05). Patients with double major curve were found to have the lowest bracing failure rate (19.4%), but there was no significant difference compared with other curve patterns. Bracing failure rate was marked higher in individual with genotype GG (66.7%) than that with genotype AA or AG.

CONCLUSIONSProgression of most mild or moderate AIS can be managed by early standardized bracing treatment. It is shown that large initial Cobb angle and genotype GG of matrilin-1 gene are indicative of less bracing effectiveness.

Adolescent ; Braces ; Cartilage Oligomeric Matrix Protein ; Child ; Extracellular Matrix Proteins ; genetics ; Female ; Follow-Up Studies ; Genotype ; Glycoproteins ; genetics ; Humans ; Matrilin Proteins ; Polymorphism, Genetic ; Prospective Studies ; Scoliosis ; genetics ; therapy ; Treatment Outcome

OBJECTIVETo investigate the association of matrilin-1 gene polymorphisms with adolescent idiopathic scoliosis (AIS) risk.

METHODSThis study population consisted of 419 patients with AIS and 460 healthy controls. The maximum Cobb angle of AIS patients was recorded. For initial screening, the 7 tagSNPs were genotyped in 197 cases and 172 controls. Next, we validated any significant associations in additional sample of 222 cases and 288 controls. Single-marker and haplotype analysis were employed. Genotyping was performed by PCR-RFLP method.

RESULTSWe found that allele G of rs1149048 was a significant predisposition allele of AIS (P = 0.0027, OR = 1.34 within 95% CI = 1.11 approximately 1.62), and individuals with genotype GG had a higher risk for AIS compared to AA + AG (P = 0.0008, OR = 1.61 within 95% CI = 1.22 approximately 2.12). Polymorphism of rs1149048 was also associated with curve severity in AIS patients. And a significantly higher in maximum Cobb angle was found in patients with GG genotype (P = 0.002).

CONCLUSIONSIt is concluded that the tagSNP rs1149048 polymorphism in the MATN1 promoter region is associated with both susceptibility and disease severity in AIS.

Adolescent ; Cartilage Oligomeric Matrix Protein ; Case-Control Studies ; Child ; Extracellular Matrix Proteins ; genetics ; Female ; Follow-Up Studies ; Genetic Predisposition to Disease ; Genotype ; Glycoproteins ; genetics ; Humans ; Linkage Disequilibrium ; Male ; Matrilin Proteins ; Polymorphism, Single Nucleotide ; Scoliosis ; genetics ; Young Adult

OBJECTIVESTo study cartilage oligomeric matrix protein (COMP) mRNA and protein expression in normal pancreas, chronic pancreatitis (CP), and pancreatic cancer tissues.

METHODSTissues from 15 cases of normal pancreas, 14 cases of chronic pancreatitis and 14 cases of pancreatic cancer were analyzed by Northern blot, Western blot, in situ hybridization and immunohistochemistry.

RESULTSCOMP mRNA signals and immunoreactivity were strongly present in the cytoplasm of degenerating acinar cells in CP tissues as well as in CP-like lesions in pancreatic cancer tissues. In contrast, COMP expression was weak to absent in the cytoplasm of cancer cells in pancreatic cancer tissues, and in ductal cells and islet cells in normal pancreatic tissues.

CONCLUSIONCOMP is preferentially expressed in degenerating acinar cells in CP and in CP-like areas in pancreatic cancer, suggesting a potential role of this molecular in acinar cell dysfunction in CP.

Blotting, Northern ; Blotting, Western ; Cartilage Oligomeric Matrix Protein ; Dimerization ; Extracellular Matrix Proteins ; chemistry ; genetics ; metabolism ; Glycoproteins ; chemistry ; genetics ; metabolism ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Matrilin Proteins ; Pancreas ; metabolism ; pathology ; Pancreatic Neoplasms ; metabolism ; pathology ; Pancreatitis, Chronic ; metabolism ; pathology ; RNA, Messenger ; genetics ; metabolism

OBJECTIVETo determine the circulating matrilin-1 levels in adolescent idiopathic scoliosis (AIS), and to investigate its potential role in etiopathogenisis of AIS.

METHODSThis study population consisted of 25 patients with AIS from June 2006 to March 2007 and 25 age-matched normal controls. All subjects of the study met the following criteria: no evidence of bone diseases, metabolic diseases or growth disturbances; no evidence of systemic illness or other condition known to affect bone metabolism; and no history of recent steroid intake and surgery of congenital cardiopathy. The maximum Cobb angle and curve pattern of AIS group were recorded. All AIS patients were categorized by progressive and non-progressive groups. Progression to a severe curve was defined per usual clinical criteria (progression to a > 40 degrees curve in an individual still growing or progression to a > 50 degrees curve in an adult). Measurements of genotype by PCR-RFLP methods and circulating matrilin-1 by ELISA assay were performed in both AIS and control groups. The circulating matrilin-1 levels were compared between AIS and control groups, and also among different genotype individuals. The relationship between matrilin-1 levels and cure progression were also analyzed.

RESULTSCompared with control group, a marked decrease of plasma matrilin-1 levels was found in AIS groups (P = 0.0002). Matrilin-1 levels of both AIS and control groups with GG genotype tended to be lower than with AA and AG genotypes, and this trend was stronger in AIS groups. Compared with non-progressive AIS group, plasma matrilin-1 levels in progressive AIS group were significantly lower.

CONCLUSIONSThere is an association between matrilin-1 levels and curve progression. Measurement of circulating matrilin-1 levels is helpful for early screening and diagnosis of AIS, and it may be considered as an independent index to predict curve progression.

Adolescent ; Adult ; Cartilage Oligomeric Matrix Protein ; Child ; Extracellular Matrix Proteins ; blood ; genetics ; Female ; Follow-Up Studies ; Genotype ; Glycoproteins ; blood ; genetics ; Humans ; Male ; Matrilin Proteins ; Scoliosis ; blood ; diagnosis ; Young Adult

Cartilage oligomeric matrix protein-angiopoietin-1 (COMP-Ang1) is an angiogenic factor for vascular angiogenesis. The aim was to investigate the effect of an intracavernosal injection of COMP-Ang1 on cavernosal angiogenesis in a diabetic rat model. Male Otsuka Long-Evans Tokushima Fatty (OLETF) rats made up the experimental group (1 yr old) and Long-Evans Tokushima Otsuka (LETO) rats made up the control group. The experimental group was divided into vehicle only, 10 microg COMP-Ang1, and 20 microg COMP-Ang1. COMP-Ang1 was injected into the corpus cavernosum of the penis. After 4 weeks, the penile tissues of the rats were obtained for immunohistochemistry and Western blot analysis. The immunoreactivity of PECAM-1 and VEGF was increased in the COMP-Ang1 group compared with the vehicle only group. Moreover, the expression of PECAM-1 and VEGF was notably augmented in the 20 microg Comp Ang-1 group. In the immunoblotting study, the expression of PECAM-1 and VEGF protein was significantly less in the OLEFT rats than in the control LETO rats. However, this expression was restored to control level after intracavernosal injection of COMP-Ang1. These results show that an intracavernosal injection of COMP-Ang1 enhances cavernous angiogenesis by structurally reinforcing the cavernosal endothelium.
Angiopoietin-1/genetics/*metabolism ; Animals ; Antigens, CD31/metabolism ; Blood Glucose/analysis ; Blotting, Western ; Body Weight ; Cartilage Oligomeric Matrix Protein/genetics/*metabolism ; Diabetes Mellitus, Experimental/*pathology ; Immunohistochemistry ; Male ; Neovascularization, Physiologic/*drug effects ; Penis/metabolism/pathology ; Rats ; Rats, Long-Evans ; Recombinant Fusion Proteins/biosynthesis/genetics/*pharmacology ; Vascular Endothelial Growth Factor A/metabolism