Glycosaminoglycan linkage region of urinary bikunin as a potentially useful biomarker for β3GalT6‐deficient spondylodysplastic Ehlers–Danlos syndrome

Abstract

The spondylodysplastic type of Ehlers–Danlos syndrome (spEDS) is caused by genetic defects in the B4GALT7 or B3GALT6 genes both deranging the biosynthesis of the glycosaminoglycan linkage region of chondroitin/dermatan sulfate and heparan sulfate proteoglycans. In this study, we have analyzed the linkage regions of urinary chondroitin sulfate proteoglycans of three siblings, diagnosed with spEDS and carrying biallelic pathogenic variants of the B3GALT6 gene. Proteoglycans were digested with trypsin, glycopeptides enriched on anion‐exchange columns, depolymerized with chondroitinase ABC, and analyzed by nLC‐MS/MS. In urine of the unaffected mother, the dominating glycopeptide of bikunin/protein AMBP appeared as only one dominating (99.9%) peak with the canonical tetrasaccharide linkage region modification. In contrast, the samples of the three affected siblings contained two different glycopeptide peaks, corresponding to the canonical tetrasaccharide and to the non‐canonical trisaccharide linkage region modifications in individual ratios of 61/38, 73/27, and 59/41. We propose that the relative distribution of glycosaminoglycan linkage regions of urinary bikunin glycopeptides may serve as a phenotypic biomarker in a diagnostic test but also as a biomarker to follow the effect of future therapies in affected individuals.

A High-Quality Chromosome-Level Genome Assembly of a Snail Cipangopaludina cathayensis (Gastropoda: Viviparidae)

“…Figure 4C,D show the GO and KEGG enrichment of the positive selective genes, respectively. Five putative genes that appeared to be positively selected in C. cathayensis In C. cathayensis, we found an expansion gene slc4a2 and a positive gene b3galt6, which were, respectively, related to digestion [49] and bone development [50]. These findings may suggest that C. cathayensis has strong digestive and shell formation abilities in order to adapt well to various environments.…”

A biological guide to glycosaminoglycans: current perspectives and pending questions

“…In contrast, only the tetrasaccharide was found in the urinary bikunin of their unaffected mother. The linkage region of urinary bikunin could thus be a marker for the b-3GalT6-deficient syndrome [107]. In a b3galt6 knockout zebrafish model, associated with a decrease in GAG content and disorganized collagen fibrils, a small amount of PGs contain a trisaccharide linker [108].…”