Abstract
The CHST14 gene, localized at 15q14, is a single exon gene with an open reading frame of 1131 base pairs, encoding a 43 kDa protein dermatan-4-O-sulfotransferase-1 (D4ST1) that catalyzes the 4-O-sulfation of N-acetyl-D-galactosamine residues in dermatan sulfate (DS). Both nearly exhaustively desulfated DS and partially desulfated DS serve as excellent substrates for the enzyme. Chst14/D4st1-deficient mice showed growth retardation as well as multiple system abnormalities including neurology such as decreased neurogenesis and diminished proliferation of neural stem cells. Recently, recessive loss-of-function mutations in the CHST14 gene were found to cause a specific form of Ehlers-Danlos syndrome (EDS) designated as D4ST1-deficient EDS (DD-EDS). The disorder is characterized by progressive multisystem fragility-related manifestations (skin hyperextensibilty and fragility, progressive spinal and foot deformities, large subcutaneous hematoma) and various malformations (facial features, congenital eye/heart/gastrointestinal defects, congenital multiple contractures). Glycosaminoglycan (GAG) chains from the affected skin fibroblasts were composed of a negligible amount of DS and excess chondroitin sulfate (CS), which was suggested to result from an impaired lock by 4-O-sulfation due to D4ST1 deficiency followed by back epimerization from L-iduronic acid to D-glucuronic acid. GAG chains of decorin from the affected skin fibroblasts were composed exclusively of CS and no DS, the opposite features observed in normal controls. Thus, skin fragility in the disorder was supposed to be caused by impaired assembly of collagen fibrils mediated by decorin bearing a CS chain that replaced a DS chain. The disorder stresses the importance of the role of CHST14/D4ST1 and DS in human development and maintenance of extracellular matrices.
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Kosho, T., Mizumoto, S., Sugahara, K. (2014). Carbohydrate (N-Acetylgalactosamine 4-O) Sulfotransferase 14 (CHST14). In: Taniguchi, N., Honke, K., Fukuda, M., Narimatsu, H., Yamaguchi, Y., Angata, T. (eds) Handbook of Glycosyltransferases and Related Genes. Springer, Tokyo. https://doi.org/10.1007/978-4-431-54240-7_156
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DOI: https://doi.org/10.1007/978-4-431-54240-7_156
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