Compound phenotype of osteogenesis imperfecta and Ehlers–Danlos syndrome caused by combined mutations inCOL1A1andCOL5A1

Abstract

Osteogenesis imperfecta (OI) is an inherited connective tissue disorder with a broad clinical spectrum that can overlap with Ehlers–Danlos syndrome (EDS). To date, patients with both OI and EDS have rarely been reported. In the present study, we investigated a family with four members, one healthy individual, one displaying OI only, and two displaying the compound phenotype of OI and EDS, and identified the pathogenic mutations. Whole exome sequencing was applied to the proband and her brother. To verify that the mutations were responsible for the pathogenesis, conventional Sanger sequencing was performed for all members of the family. We identified a known COL1A1 (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 COL5A1 (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. The results of the present study suggested that the proband and her mother presented with the compound OI–EDS phenotype caused by pathogenic mutations in COL5A1 and COL1A1.

Integrative analyses of genetic characteristics associated with skeletal endothelial cells

“…Type V collagen, translated by the Col5a1 and Col5a2 genes, controls the assembly of fibrils and contributes to the composition of the bone matrix (29,30). Disruptions in Col5a1 have been implicated in the pathogenesis of osteogenesis imperfecta (31,32). Our investigation revealed an inverse relationship between the transcriptional levels of Adamts1, Adamts2, Adamts4, Adamts14, Col5a1, and Col5a2 in femoral ECs and advancing age, thereby confirming their involvement in the age-related deterioration of the bone vascular network.…”

COL5A1 RS12722 Is Associated with Temporomandibular Joint Anterior Disc Displacement without Reduction in Polish Caucasians

“…Evaluation of these mutations by in silico tools indicates their pathogenicity. A similar study by Lin et al investigated the co-occurrence of EDS and osteogenesis imperfecta (OI) in Chinese families [20]. Their results suggest that a combination of COL5A1 and COL1A1 mutations may lead to compound phenotypes of OI and EDS, while COL1A1 (c.2010delT) may result in OI.…”

Next-Generation Sequencing of Connective Tissue Genes in Patients with Classical Ehlers-Danlos Syndrome

“…The next group included patients with COL1A1 and COL1A2 gene variants, which, in addition to COL5A1 and COL5A2, are well-known causes of cEDS or cEDS overlapping with OI [12][13][14]. We found three patients with likely pathogenic, VUS, and benign variants in COL1A1 and six patients with VUS variants in COL1A2.…”