A large kindred with EDS type IV was studied clinically, and the biochemical defects and underlying mutation in the COL3A1 gene that encodes the chains of type III procollagen were identified.
Although vascular Ehlers-Danlos syndrome appears to be genetically homogeneous, allelic heterogeneity is marked, and the natural history varies with gender and type of mutation in COL3A1.
Aortic dilatation/dissection (AD) can occur spontaneously or in association with genetic syndromes, such as Marfan syndrome (MFS; caused by FBN1 mutations), MFS type 2 and Loeys-Dietz syndrome (associated with TGFBR1/TGFBR2 mutations), and Ehlers-Danlos syndrome (EDS) vascular type (caused by COL3A1 mutations).
Based on the previous finding that mutations in COL3A1 cause type IV EDS, our study indicates a possible common pathological pathway linking connective tissue diseases and brain malformations.
Thus, in contrast to mutations in genes that encode the dominant protein of a tissue (e.g., COL1A1 and COL2A1), in which "null" mutations result in phenotypes milder than those caused by mutations that alter protein sequence, the phenotypes produced by these mutations in COL3A1 overlap with those of the vascular form of EDS.
We describe the phenotype of the largest series of vEDS patients with glutamic acid to lysine substitutions (Glu>Lys) in COL3A1, which were all previously considered to be variants of unknown significance.
Thus, in contrast to mutations in genes that encode the dominant protein of a tissue (e.g., COL1A1 and COL2A1), in which "null" mutations result in phenotypes milder than those caused by mutations that alter protein sequence, the phenotypes produced by these mutations in COL3A1 overlap with those of the vascular form of EDS.
The primary suspicion of vascular EDS with the unsatisfactory identification of a COL3A1 benign variant was secondarily readjusted with the identification of COL1A1 p.(Arg312Cys) variant.
Vascular Ehlers Danlos syndrome (EDS) is a rare autosomal dominant inherited disorder of connective tissue resulting from mutation of the COL3A1 gene encoding type III collagen.
The sequence of the COL3A1 gene from the patients with EDS type IV-like alterations of the connective tissue morphology was analyzed.No mutation was detected.
We have used a number of restriction site dimorphisms, tightly linked to the structural genes of type I collagen (COL1A1 COL1A2) and type III collagen (COL3A1), to investigate the segregation of corresponding alleles in three pedigrees in which type II EDS was clearly inherited as a dominant trait.
Ehlers-Danlos syndrome (EDS) type IV is a heritable disorder resulting from mutations in the COL3A1 gene that cause deficient production of type III collagen.
Identical G+1 to A mutations in three different introns of the type III procollagen gene (COL3A1) produce different patterns of RNA splicing in three variants of Ehlers-Danlos syndrome. IV. An explanation for exon skipping some mutations and not others.
A single-base mutation in intron 37 of the gene for type III procollagen (COL3A1) was found in a proband with the type IV variant of Ehlers-Danlos syndrome.