Type 2 Atelostogénesis (atelosteogenesis type 2) - Gen DTDST (= SLC26A2)

Type 2 (AO2) atelostogénesis is a congenital disease that is part of the family of chondrodysplasia or skeletal dysplasias. It is considered a severe variant of diastrophic dysplasia (DTD) and, although in the usual classifications not reach the severity of type 1B achondrogenesis, also it has a high incidence prenatal and postnatal death from respiratory failure. It is characterized by a large limb shortening, narrow thorax, prominent and rounded abdomen, cleft palate and sometimes presents, as occurs in cases of DTD, called "finger autoestopista".

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 type 2 atelostogénesis and other skeletal dysplasias.

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.

Have identified at least eight mutations SLC26A2 gene in people with atelosteogenesis type 2. Generally, affected individuals have a mutation in one copy of the gene that alters the normal structure of the SLC26A2 protein, and a mutation in the other copy of the gene which inhibits any functional protein coding. A common mutation causes type 2 atelosteogenesis replaces the amino acid arginine by tryptophan at amino acid position 279 in the protein (or Arg279Trp R279W). In the Finnish population, the most frequent mutation (IVS1 + 2T> C) interferes with the normal process of the SLC26A2 protein. SLC26A2 gene mutations alter the structure and function of the carrier protein SLC26A2, causing a reduction or defect in the uptake and transport of sulfate. This reduction of sulfate transport in chondrocytes leads to low sulfation of proteoglycans, which in turn generates an abnormal cartilage formation.

Although the exact mechanisms are unknown, given the rarity of the process and the existence of comparable individuals together, 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 gravity, as in the case of type 2 (AO2) atelostogénesis, would have an intermediate transport layer sulfate.

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 performed in IVAMI: in IVAMI perform detection of mutations associated conatelostogénesis type 2 (AO2), and other skeletal dysplasias, 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).