Three PSACH patients in this family (individuals III-3, III-5, and IV-3) were heterozygous for the nucleotide change c.1675G>A (Figure 1(b)) in exon 15, which is located at the CTD of COMP.
As shown in Table 1, the mean plasma COMP concentrations of three PSACH patients with COMP mutation was 65.33 [+ or -] 13.37 ng/ml, which was significantly lower than the concentrations of age-matched controls, 154.14 [+ or -] 19.69 ng/ml (P < 0.001).
In this study, we report a PSACH family with six affected members in Southwest China.
There is evidence that peripheral blood COMP levels decrease in PSACH patients with COMP mutations, but circulating COMP levels in asymptomatic carrier have not been reported [14, 15].
Since plasma COMP levels in PSACH patients were decreased, we hypothesized CTX-II levels in those PSACH patients would increase, thus exploring another potential biomarker.
Early electron microscopy studies of PSACH iliac crest biopsies showed dilated rough endoplasmic reticulum (rER) in chondrocyte .
In summary, our findings expand the spectrum of mutations in COMP leading to PSACH. We illustrate that the novel mutation (Glu559Lys) changes the secondary structure of COMP, which possibly leads to misfolding and intracellular retention of mutant COMP proteins.
Vertel, "COMP mutations: domain-dependent relationship between abnormal chondrocyte trafficking and clinical PSACH and MED phenotypes," Journal of Cellular Biochemistry, vol.
(a) Plasma COMP levels in PSACH were significantly lower than the age-matched controls, and plasma COMP levels in normal adult controls were significantly higher than normal children less than three years old.
There is also substantially less epiphyseal involvement as compared with those with PSACH.
Patients with PSACH usually present at 2 to 4 years of age with abnormal gait or extremities and are subsequently noted to have a shortened stature and disproportionately shortened limbs.
Individuals have a normal life span and intelligence, and there are no known extraskeletal manifestations related to PSACH. The most prominent feature of this disease relates to the morbidity from early degenerative joint disease, and individuals with PSACH very often undergo joint replacement surgery for degenerative joint disease.