Diastrophic dysplasia (Diastrophic dysplasia) - Gen DTDST (SLC26A2)
Diastrophic dysplasia (DTD) is a congenital disease that is part of the family of chondrodysplasia or skeletal dysplasias, of which implies possibly the mildest form. It is characterized by short stature, joint contractures, cleft palate, external ear swelling and called "finger autoestopista". Signs and symptoms of diastrophic dysplasia are similar to those of other skeletal disorder called type 2 atelosteogenesis; However, Diastrophic dysplasia tends to be less severe. Although some affected infants have respiratory problems, most people with dysplasia Diastrophic live to adulthood.
Mutations in the gene DTDST ( "Diastrophic Dysplasia Sulfate Transporter"), also called SLC26A2, located on the long arm of chromosome 5 (5q32-q33.1) are responsible for the diastrophic dysplasia and other skeletal dysplasias - see Achondrogenesis type 1B, type 2 Atelosteogenesis and multiple epiphyseal dysplasia.
The SLC26A2 gene encodes a protein that carries sulfate ions across cell membranes. This protein appears to be active in many body tissues, including cartilage development. Cartilage cells using sulfate ion to form proteoglycans. These molecules help give cartilage its consistency. Because sulfate ions required for proteoglycans, the transport activity of the SLC26A2 protein is essential for normal cartilage formation.
They have identified more than 20 mutations in the SLC26A2 gene in people with Diastrophic dysplasia. People with diastrophic dysplasia usually have a mutation in one gene copy that alters the normal structure of the SLC26A2 protein and a mutation in the other copy of the gene encoding inhibits any functional protein. These genetic changes disrupt the ability of cartilage cells to use sulfate ions necessary. Without sufficient sulfate, the cell is unable to produce normal proteoglycan. The deficiency of these essential molecules affects cartilage structure and the formation and growth of normal bone.
Although the exact mechanisms are unknown, given the difficulty of the process and obtaining comparable between individuals, it is believed that differences in the severity of skeletal dysplasias are a reflection of the difference in uptake of residual sulfate through sulfate transporter DTDST mutated. Thus, cells of patients with achondrogenesis type 1B have a sulfate transport with no or minimal, being the most serious condition, while milder chondrodysplasias as diastrophic dysplasia and multiple epiphyseal dysplasia (MED), They have increased transport of sulfate; the intermediate intensity (atelosteogenesis type 2), meanwhile, have a level intermediate transport sulfate.
This hypothesis is based on the studies that indicate that there is a correlation, although not absolute, including point mutations in the gene DTDST and clinical phenotypes different chondrodysplasias. Thus, in the most severe chondrodysplasia, the ACG1B, it is believed that the consequences of genetic abnormalities are dramatic for protein structure, while for the less severe forms, such as diastrophic dysplasia, a less severe structural changes are anticipated . However, there are also other factors that may modulate the severity of the disease, such as environmental influences or the ability to use alternative to transport routes sulfate, which explains the relative phenotypic variability exists.
This disease is inherited in an autosomal recessive pattern, that is, both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.
Tests in IVAMI: in IVAMI perform detection of mutations associated with diastrophic dysplasia (DTD), by complete PCR amplification of exons DTDST gene (SLC26A2) and subsequent sequencing.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample) if postnatal diagnosis. For prenatal diagnosis, chorionic villus sampling.