Ehlers-Danlos syndrome type IV: A single base substitution of the last nucleotide of exon 34 in COL3A1 leads to exon skipping

The Ehlers-Danlos syndrome has been classified into nine phenotypic presentations. Type IV is a variant of particular importance because people affected with this genodermatosis are at great risk of spontaneous hemorrhage from vascular rupture or bowel perforation. Recent molecular advances have identified mutations in the gene for type III procollagen as responsible for Ehlers-Danlos syndrome type IV. We report a case of a 14-year-old male with a typical presentation of the type IV variant who was found to have markedly dilated fibroblast cisternae and varying collagen fibril diameter on ultrastructural study. A novel genetic defect was noted by polymerase chain reaction and DNA sequencing of genetic material isolated from skin fibroblast cultures. Analysis of the gene for type III procollagen revealed a single base mutation in the last nucleotide of exon 34. The mutation led to abnormal RNA splicing and skipping of exon 34 on the mRNA level.