Genotype-phenotype correlation in vascular Ehlers-Danlos syndrome: Novel duplication mutation of COL3A1 gene in a large pedigree

M. Medvecz, Gy. Fekete, B. Mayer, S. Kárpáti

Vascular Ehlers-Danlos syndrome (vEDS, OMIM 130050) is a rare autosomal dominantly inherited connective tissue disorder characterized by generalized connective tissue fragility. Affected individuals are at risk of arterial rupture, aneurysm, or dissection; gastrointestinal perforation or rupture; and uterine rupture during pregnancy. The disease is caused by structural defects in the proα1(III) chain of collagen type III encoded by the COL3A1 gene. Here we present a vEDS patient with complex severe clinical symptoms, and data of full-gene Sanger sequencing of COL3A1 revealing a previously unreported heterozygous variant, c.3124_3141dup (p.Ala1042_Gly1047dup). The duplication of that 18 bp causes duplication of 6 residues including two glycines within the triplehelical region (Ala-Pro-Gly-Ala-Pro-Gly). The novel duplication mutation co-segregated with the vEDS-phenotype in the large family of the index patient. This previously unpublished insertion in the COL3A1gene expands the spectrum of mutations underlying vEDS and helps to perform genetic counselling.