Recessive MED with auricular swelling due to compound heterozygosity Arg279Tpr/Thr512Lys in the SLC26A2 gene

摘要

Mutations in the diastrophic dysplasia (DTD) sulfate transporter gene (SLC26A2) result in a family of skeletal dysplasias, which range in severity from lethal conditions including achondrogenesis type IB (ACG1B), atelosteogenesis type 2 (AO2), and de la Chapelle dysplasia (DLCD) to less severe, non-lethal conditions such as DTD and recessive multiple epiphyseal dysplasia [rMED; Hastbacka et al, 1996; Superti-Furga et al., 1996a, 1996b; 1999, Bonafe et al., 2008]. The gene encodes a sulfate-chloride exchanger of the cell membrane [Hastbacka et al., 1994]. Structural mutations which completely abolish the sulfate transporter activity on both alleles of the SLC26A2 cause the severe lethal phenotypes whereas compound hetero2ygosity of null alleles with missense mutations or other types of mutations preserving residual transporter activity cause milder phenotypes. Intermediate phenotypes sometimes difficult to classify exist between lethal AO2 and severe DTD, or between mild DTD and rMED, and these are usually found in patients with compound heterozygous mutations [Bonafe et al., 2008; Czarny-Ratajczak et al., 2010].