ClinVar

In a Pakistani sister and brother with the musculocontractural type of Ehlers-Danlos syndrome (EDSMC1; 601776), originally reported by Steinmann et al. (1975), Janecke et al. (2015) identified homozygosity for a duplication (c.453dup) in the CHST14 gene, causing a frameshift predicted to result in a premature termination codon (CYS152LeufsTer10). The unaffected parents were heterozygous for the mutation. Cultured dermal fibroblasts from the patients showed lack of a reticular extracellular matrix (ECM) of fibronectin (FN1; 135600) and tenascins (see 187380), and the level of tenascins was markedly reduced compared with control fibroblasts. Patient fibroblasts lacked decorin (DCN; 125255) and thrombospondin (see 188060) fibrils in the extracellular environment, and lacked the fibronectin and fibrillar collagen receptors alpha-5-beta-1 (ITGB1; 135630) and alpha-2-beta-1 (ITGA2; 192974), respectively, on the cell surface. Mutant cells showed intracellular retention of collagen types I (see 120150) and III (see 120180), and reduced deposition of collagen types I, III, V (see 120215), and VI (see 120220) fibrils in the ECM, compared to controls; mutant cells also produced and stored higher amounts of chondroitin sulfate glycosaminoglycans in the cytoplasm, which was not organized in the ECM.