Description of Joint Alterations Observed in a Family Carrying p.Asn453Ser COMP Variant: Clinical Phenotypes, In Silico Prediction of Functional Impact on COMP Protein and Stability, and Review of the Literature.

The role of genetics in the development of osteoarthritis is well established but the molecular bases are not fully understood. Here, we describe a family carrying a germline mutation in COMP (Cartilage Oligomeric Matrix Protein) associated with three distinct phenotypes. The index case was enrolled for a familial form of idiopathic early-onset osteoarthritis. By screening potential causal genes for osteoarthritis, we identified a heterozygous missense mutation of COMP (c.1358C>T, p.Asn453Ser), absent from genome databases, located on a highly conserved residue and predicted to be deleterious. Molecular dynamics simulation suggests that the mutation destabilizes the overall COMP protein structure and consequently the calcium releases from neighboring calcium binding sites. This mutation was once reported in the literature as causal for severe multiple epiphyseal dysplasia (MED). However, no sign of dysplasia was present in the index case. The mutation was also identified in one of her brothers diagnosed with MED and secondary osteoarthritis, and in her sister affected by an atypical syndrome including peripheral inflammatory arthritis of unknown cause, without osteoarthritis nor dysplasia. This article suggests that this mutation of COMP is not only causal for idiopathic early-onset osteoarthritis or severe MED, but can also be associated to a broad phenotypic variability with always joint alterations.

Voltammetric Sensor Based on Molecularly Imprinted Chitosan-Carbon Nanotubes Decorated with Gold Nanoparticles Nanocomposite Deposited on Boron-Doped Diamond Electrodes for Catechol Detection.

Phenolic compounds such as catechol are present in a wide variety of foods and beverages; they are of great importance due to their antioxidant properties. This research presents the development of a sensitive and biocompatible molecular imprinted sensor for the electrochemical detection of catechol, based on natural biopolymer-electroactive nanocomposites. Gold nanoparticle (AuNP)-decorated multiwalled carbon nanotubes (MWCNT) have been encapsulated in a polymeric chitosan (CS) matrix. This chitosan nanocomposite has been used to develop a molecular imprinted polymers (MIP) in the presence of catechol on a boron-doped diamond (BDD) electrode. The structure of the decorated MWCNT has been studied by TEM, whereas the characterization of the sensor surface has been imaged by AFM, demonstrating the satisfactory adsorption of the film and the adequate coverage of the decorated carbon nanotubes on the electrode surface. The electrochemical response of the sensor has been analyzed by cyclic voltammetry (CV) where excellent reproducibility and repeatability to catechol detection in the range of 0 to 1 mM has been found, with a detection limit of 3.7 × 10-5 M. Finally, the developed sensor was used to detect catechol in a real wine sample.