Congenital joint dislocations caused by carbohydrate sulfotransferase 3 deficiency in recessive Larsen syndrome and humero-spinal dysostosis.

Deficiency of carbohydrate sulfotransferase 3 (CHST3; also known as chondroitin-6-sulfotransferase) has been reported in a single kindred so far and in association with a phenotype of severe chondrodysplasia with progressive spinal involvement. We report eight CHST3 mutations in six unrelated individuals who presented at birth with congenital joint dislocations. These patients had been given a diagnosis of either Larsen syndrome (three individuals) or humero-spinal dysostosis (three individuals), and their clinical features included congenital dislocation of the knees, elbow joint dysplasia with subluxation and limited extension, hip dysplasia or dislocation, clubfoot, short stature, and kyphoscoliosis developing in late childhood.

A quantitative and qualitative method for direct 2-DE analysis of murine cartilage.

Direct 2-DE analysis of cartilage is difficult due to the high proteoglycan content. Proteoglycan removal before IEF may however cause the partial or total loss of specific proteins making this approach ineffective when quantitative data are required to investigate protein expression differences. Thus, we have developed a 2-DE method including passive rehydration loading that does not require sample pretreatment and allows direct protein expression studies in cartilage samples.

In vivo contribution of amino acid sulfur to cartilage proteoglycan sulfation.

Cytoplasmic sulfate for sulfation reactions may be derived either from extracellular fluids or from catabolism of sulfur-containing amino acids and other thiols. In vitro studies have pointed out the potential relevance of sulfur-containing amino acids as sources for sulfation when extracellular sulfate concentration is low or when its transport is impaired such as in DTDST [DTD (diastrophic dysplasia) sulfate transporter] chondrodysplasias. In the present study, we have considered the contribution of cysteine and cysteine derivatives to in vivo macromolecular sulfation of cartilage by using the mouse model of DTD we have recently generated [Forlino, Piazza, Tiveron, Della Torre, Tatangelo, Bonafe, Gualeni, Romano, Pecora, Superti-Furga et al.

A diastrophic dysplasia sulfate transporter (SLC26A2) mutant mouse: morphological and biochemical characterization of the resulting chondrodysplasia phenotype.

Mutations in the diastrophic dysplasia sulfate transporter (DTDST or SLC26A2) cause a family of recessively inherited chondrodysplasias including, in order of decreasing severity, achondrogenesis 1B, atelosteogenesis 2, diastrophic dysplasia (DTD) and recessive multiple epiphyseal dysplasia. The gene encodes a widely distributed sulfate/chloride antiporter of the cell membrane whose function is crucial for the uptake of inorganic sulfate, which is needed for proteoglycan sulfation. To provide new insights in the pathogenetic mechanisms leading to skeletal and connective tissue dysplasia and to obtain an in vivo model for therapeutic approaches to DTD, we generated a Dtdst knock-in mouse with a partial loss of function of the sulfate transporter.

High-performance liquid chromatography and capillary electrophoresis: methodological challenges for the determination of biologically relevant low-aliphatic aldehydes in human saliva.

Tobacco smoke is involved in the pathogenesis of cardiovascular and respiratory diseases and also has a local toxic effect in the oral cavity. Low-aliphatic aldehydes, such as formaldehyde, acetaldehyde and acrolein, are among the main components of mainstream cigarette smoke and their local noxious and carcinogenic effects in the oral cavity and upper gastrointestinal tract are well-known. Although various studies have been performed so far to determine their content in cigarette smoke, none has included the direct measurement of these compounds in the saliva of smoking and nonsmoking subjects.