Disease gene identification of a new type of Ehlers-Danlos syndrome

我们发现CHST14是一种新型常染色体隐性埃勒斯-丹洛斯综合征（EDS）的致病基因。CHST14编码皮肤4- o -硫转移酶1 (D4ST1)，将活性硫酸盐转移到皮肤上。在患者中观察到的突变体中，其酶活性几乎完全丧失，胶原纤维组装的关键调节因子decorin蛋白聚糖的皮肤硫酸酯在患者的成纤维细胞中完全丧失，并被硫酸软骨素（CS）所取代。这可能表明，不耐受机械压迫的不灵活CS的替代导致胶原束形成受损。

We identified CHST14 as a disease gene for the novel autosomal recessive Ehlers-Danlos syndrome (EDS). CHST14 encodes dermatan 4-O-sulfotransferase 1 (D4ST1), which transfers active sulfate to dermatan. In the mutants observed in the patients, its enzyme activity was almost completely lost and dermatan sulfate of decorin proteoglycan, a key regulator of collagen fibril assembly, was completely lost and replaced by chondroitin sulfate (CS) in the patients' fibroblasts. This may suggest that the replacement to inflexible CS, which intolerant to the mechanical compression, resulted in the impaired collagen bundle formation.