Deficiencies are associated with many forms of osteochondrodysplasia. These include: * achondrogenesis type 1B * diastrophic dysplasia * atelosteogenesis, type II * recessive multiple epiphyseal dysplasia Correlation between genotype and phenotype Since its first description, over 30 mutations in the SLC26A2 gene have been described in the four recessively inherited chondrodysplasias listed above. Achondrogenesis 1B (ACG-1B) is the most severe form of these chondrodysplasias, resulting in skeletal underdevelopment and death preceding or shortly after birth. Atelosteogenesis type II (AO-II) can be lethal in the neonatal period, whereas diastrophic dysplasia (DTD) and autosomal recessive multiple epiphyseal dysplasia (EDM4/rMED) are considered to be the least severe forms. When ten previously described SLC26A2 mutation were expressed in mammalian cells, a strong correlation was found between the amount of<unk>  transport activity of the mutated protein and the severity of the phenotype in patients where these mutations have been identified. For example, a mutation that results in a non-functional protein on both alleles was always found with the severe ACG-IB phenotype, but non-functional mutations on both alleles were never found with the less severe phenotypes, DTD and rMED. Mutations found in the moderately severe AO-II phenotype were always the result of a non-functioning mutation on one allele and a partial-functioning mutation on the opposite allele. In contrast, mutations described in the mildest form of the chondrodysplasia, rMED, result in proteins that retain at least some partial<unk>  transport function on both alleles. This suggests that even a small amount of SLC26A2-mediated<unk>  transport in chondrocytes can mitigate the clinical severity of the chondrodysplasia. However, a less predictable genotype/phenotype correlation has been found with a mutation described predominately in the Finnish population. This Finnish mutation is located in the splice site of the gene and results in low SLC26A2 mRNA levels. Different levels of expression of the SLC26A2 protein is probably the cause of the variable phenotypes described with this mutation.
Sulfate transporter
Carboxylate transporter
Sodium-chloride symporter
Thiamine transporter 1
Norepinephrine transporter
Angiotensin-converting enzyme 2
Flavin containing monooxygenase 1
Flavin-containing monooxygenase 3