In 3 patients with diastrophic dysplasia (DTD; 222600) from Germany, the Netherlands, and France, respectively, Hastbacka et al. (1994) identified heterozygosity for a deletion of 1 nucleotide in codon 575 of the DTD gene (SLC26A2), converting AAG to AG; this mutation resulted in a frameshift, causing a premature translational stop after 9 codons that would eliminate the last 20% of the protein. The deletion destroyed a DdeI site and created a BfaI site, providing a simple assay for the presence of the mutation. The patients presumably carried a different DTD mutation on the other homolog. Examination of 100 normal chromosomes confirmed that the deletion was not a polymorphism.
Superti-Furga et al. (1996) found that this mutation, which they called the 1751A deletion, results in diastrophic dysplasia when compounded with the presumed reduced-expression allele frequent in Finland (606718.0010), but produces achondrogenesis type IB (ACG1B; 600972) when compounded with a second structural mutation on the other chromosome, such as N425D (606718.0006).
In a patient with atelosteogenesis type II (AO2; 256050), Hastbacka et al. (1996) identified compound heterozygosity for 1751delA and an 862C-T transition resulting in an R279W substitution (606718.0002) in the third extracellular loop.
