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

Eur J Hum Genet
Authors
Keywords
Abstract

Diastrophic dysplasia (DTD) is especially prevalent in Finland and the existence of a founder mutation has been previously inferred from the fact that 95% of Finnish DTD chromosomes have a rare ancestral haplotype found in only 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 by 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 DTDST(Fin). Unexpectedly, we found that nine of the DTD chromosomes having the apparently ancestral haplotype did not carry DTDST(Fin), but rather two other mutations. Eight such chromosomes had an R279W mutation and one had a V340del deletion. We consider the possible implications of presence of multiple DTD mutations on this rare haplotype.

Year of Publication
1999
Journal
Eur J Hum Genet
Volume
7
Issue
6
Pages
664-70
Date Published
1999 Sep
ISSN
1018-4813
DOI
10.1038/sj.ejhg.5200361
PubMed ID
10482955
Links
Grant list
AR41970 / AR / NIAMS NIH HHS / United States
HG00368 / HG / NHGRI NIH HHS / United States
HG0098 / HG / NHGRI NIH HHS / United States