Genetic Analysis of Three Korean Patients with Clinical Features of Ehlers-Danlos Syndrome Type IV

ABSTRACT

Ehlers-Danlos syndrome (EDS) is a hereditary disorder of the connective tissue. EDS type IV (EDS IV), the vascular type of the disease, is characterized by easy bruising, thin skin with visible veins, and spontaneous rupture of the large arteries, uterus, or bowel. EDS IV is caused by mutations in the gene for type III procollagen (COL3A1). However, recent studies suggest that the causative mutation of EDS IV is not homogeneous. We report our experience with three patients presenting with clinical features of type IV EDS. A 48-yr-old woman presented with acute aortic dissection (patient 1) and 36-yr-old and 21-yr-old women presented with carotidcavernous fistula (patients 2 and 3, respectively). All three patients bruised easily. Two patients (patients 1 and 3) had thin transparent skin with visible veins. Genetic analysis of COL3A1 revealed a Gly732Val (c.2195G>T) mutation in patient 1 and a duplication of 15 base pairs (c.3221_3235dup) which resulted in an interposition of five amino acids (p.Gly1074_Pro1078dup) in patient 2. However, no mutations were observed in COL3A1 or transforming growth factor beta receptors 1 and 2 in patients 3, which might be either due to a deletion of single or multiple exons in the COL3A1 gene or due to a genetic heterogeneity. This is the first report of genetically confirmed cases of EDS IV in Korea.