Identification of the Finnish founder mutation for diastrophic dysplasia (DTD)

Diastrophic dysplasia (DTD) is especially prevalent in Finland and the exis tence of a founder mutation has been previously inferred from the fact that 95% of Finnish DTD chromosomes have a rare ancestral haplotype found in on ly 4% of Finnish control chromosomes. Here we report the identification of the Finnish founder mutation as a GT->GC transition (c.-26 + 2T > C) in the splice donor site of a previously undescribed 5'-untranslated exon of the diastrophic dysplasia sulfate transporter gene (DTDST); the mutation acts b y severely reducing mRNA levels. Among 84 DTD families in Finland, patients carried two copies of the mutation in 69 families, one copy in 14 families , and no copies in one family. Roughly 90% of Finnish DTD chromosomes thus carry the splice-site mutation, which we have designated DTDSTFin. Unexpect edly, we found that nine of the DTD chromosomes having the apparently ances tral haplotype did not carry DTDSTFin, but rather two other mutations. Eigh t such chromosomes had an R279W mutation and one had a V340del deletion. We consider the possible implications of presence of multiple DTD mutations o n this rare haplotype.