Characterization of 11 new mutations in COL3A1 of individuals with Ehlers-Danlos syndrome type IV: preliminary comparison of RNase cleavage, EMC and DHPLC assays.

We report on 12 patients with EDS IV in whom clinical diagnosis was confirmed by biochemical analysis of collagen type III, and further proven by mutation analysis of the COL3A1 gene. Four overlapping RT-PCR products covering the coding sequence for the triple-helical domain of type III collagen were analyzed by direct sequencing. So far, we have identified, 4 base changes at donor splice junctions, and 1 base change at an acceptor splice site, which all affect mRNA splicing; 1 genomic deletion, which removes exon 45; and 6 nucleotide changes, which cause substitutions of glycine residues within the triple helix. Eleven of the 12 identified mutations are newly recognized. Furthermore, we report a preliminary comparison of RNase cleavage, EMC and DHPLC assays in mutation detection in the COL3A1 gene.