The proband is the fourth reported proband with Ehlers-Danlos syndrome VII with a single-base mutation that causes skipping of exon 6 in the splicing of RNA from either the COL1A1 gene or COL1A2 gene.
Heterozygous mutations in the COL1A1 or COL1A2 gene encoding the alpha1 and alpha2 chain of type I collagen generally cause either osteogenesis imperfecta or the arthrochalasis form of Ehlers-Danlos syndrome (EDS).
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 identified a known <i>COL1A1</i> (encoding collagen type I α 1 chain) mutation (c.2010delT, p.Gly671Alafs*95) in all three patients (the proband, her brother, and her mother) in this family, but also a novel heterozygous <i>COL5A1</i> (encoding collagen type V α 1 chain) mutation (c.5335A>G, p.N1779D) in the region encoding the C-terminal propeptide domain in the proband and her mother, who both had the compound phenotype of OI and EDS.
This raises the question of the association of COL1A1p.(Arg312Cys) with arterial complications and the need for a gene panel including not only the usual genes tested in search of classical or vascular EDS but also COL1A1.
Mutations near amino end of alpha1(I) collagen cause combined osteogenesis imperfecta/Ehlers-Danlos syndrome by interference with N-propeptide processing.
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.
Delineation of Ehlers-Danlos syndrome phenotype due to the c.934C>T, p.(Arg312Cys) mutation in COL1A1: Report on a three-generation family without cardiovascular events, and literature review.
Mutations in the genes coding for collagen alpha1(V) chain (COL5A1), collagen alpha2(V) chain (COL5A2), tenascin-X (TNX), and collagen alpha1(I) chain (COL1A1) have been characterized in patients with classical EDS, thus confirming the suspected genetic heterogeneity.
Molecular mechanism of alpha 1(I)-osteogenesis imperfecta/Ehlers-Danlos syndrome: unfolding of an N-anchor domain at the N-terminal end of the type I collagen triple helix.
An overlapping phenotype of Osteogenesis imperfecta and Ehlers-Danlos syndrome due to a heterozygous mutation in COL1A1 and biallelic missense variants in TNXB identified by whole exome sequencing.
In the second case, a missense mutation in COL1A1 (substitution of arginine by cysteine) results in a type I EDS phenotype with clinically normal-appearing dentition.
Ehlers-Danlos syndrome (EDS) type VII results from defects in the conversion of type I procollagen to collagen as a consequence of mutations in the substrate that alter the protease cleavage site (EDS type VIIA and VIIB) or in the protease itself (EDS type VIIC).