Structural alteration of glycosaminoglycan side chains and spatial disorganization of collagen networks in the skin of patients with mcEDS-CHST14

Publication date: Available online 13 December 2018Source: Biochimica et Biophysica Acta (BBA) - General SubjectsAuthor(s): Takuya Hirose, Naoki Takahashi, Prasarn Tangkawattana, Jun Minaguchi, Shuji Mizumoto, Shuhei Yamada, Noriko Miyake, Shujiro Hayashi, Atsushi Hatamochi, Jun Nakayama, Tomomi Yamaguchi, Ayana Hashimoto, Yoshihiro Nomura, Kazushige Takehana, Tomoki Kosho, Takafumi WatanabeAbstractMusculocontractural Ehlers-Danlos syndrome (mcEDS) due to CHST14/D4ST1 deficiency (mcEDS-CHST14) is a recently delineated type of EDS caused by biallelic loss-of-function mutations in CHST14, which results in the depletion of dermatan sulfate (DS). Clinical characteristics of mcEDS-CHST14 consist of multiple malformations and progressive fragility-related manifestations, including skin hyperextensibility and fragility. Skin fragility is suspected to result from the impaired assembly of collagen fibrils caused by alteration of the glycosaminoglycan (GAG) chain of decorin-proteoglycan (PG) from DS to chondroitin sulfate (CS). This systematic investigation of the skin pathology of patients with mcEDS-CHST14 comprised both immunostaining of decorin and transmission electron microscopy-based cupromeronic blue staining to visualize GAG chains. Collagen fibrils were dispersed in the affected papillary to reticular dermis; in contrast, they were regularly and tightly assembled in controls. Moreover, the fibrils exhibited a perpendicular arrangement to the affected epidermis, whereas fibril...
Source: Biochimica et Biophysica Acta (BBA) General Subjects - Category: Biochemistry Source Type: research