Journal
GENES
Volume 14, Issue 2, Pages -Publisher
MDPI
DOI: 10.3390/genes14020436
Keywords
musculocontractural Ehler-Danlos syndome (mcEDS); carbohydrate sulfotransferase 14 (CHST14); dermatan 4-O-sulfotransferase-1 (D4ST1); dermatan sulfate epimerase (DSE); dermatan sulfate (DS); model mouse
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Musculocontractural Ehlers-Danlos syndrome (mcEDS) is a subtype of EDS caused by mutations in the CHST14 or DSE genes, leading to loss of enzymatic activity and disruption of DS biosynthesis. Symptoms include congenital malformations and connective tissue fragility-related manifestations. Mouse models of mcEDS-CHST14 and mcEDS-DSE exhibit similar phenotypes, making them useful for research on pathophysiology and therapy.
Musculocontractural Ehlers-Danlos syndrome (mcEDS) is a subtype of EDS caused by mutations in the gene for carbohydrate sulfotransferase 14 (CHST14) (mcEDS-CHST14) or dermatan sulfate epimerase (DSE) (mcEDS-DSE). These mutations induce loss of enzymatic activity in D4ST1 or DSE and disrupt dermatan sulfate (DS) biosynthesis. The depletion of DS causes the symptoms of mcEDS, such as multiple congenital malformations (e.g., adducted thumbs, clubfeet, and craniofacial characteristics) and progressive connective tissue fragility-related manifestations (e.g., recurrent dislocations, progressive talipes or spinal deformities, pneumothorax or pneumohemothorax, large subcutaneous hematomas, and/or diverticular perforation). Careful observations of patients and model animals are important to investigate pathophysiological mechanisms and therapies for the disorder. Some independent groups have investigated Chst14 gene-deleted (Chst14(-/-)) and Dse(-/-) mice as models of mcEDS-CHST14 and mcEDS-DSE, respectively. These mouse models exhibit similar phenotypes to patients with mcEDS, such as suppressed growth and skin fragility with deformation of the collagen fibrils. Mouse models of mcEDS-CHST14 also show thoracic kyphosis, hypotonia, and myopathy, which are typical complications of mcEDS. These findings suggest that the mouse models can be useful for research uncovering the pathophysiology of mcEDS and developing etiology-based therapy. In this review, we organize and compare the data of patients and model mice.
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