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Serum bikunin isoforms in congenital disorders of glycosylation and linkeropathies
Author(s) -
Haouari Walid,
Dubail Johanne,
LounisOuaras Samra,
Prada Pierre,
Bennani Rizk,
Roseau Charles,
Huber Céline,
Afenjar Alexandra,
Colin Estelle,
VuillaumierBarrot Sandrine,
Seta Nathalie,
Foulquier François,
Poüs Christian,
CormierDaire Valérie,
Bruneel Arnaud
Publication year - 2020
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1002/jimd.12291
Subject(s) - gene isoform , chemistry , golgi apparatus , glycosylation , biochemistry , context (archaeology) , proteoglycan , keratan sulfate , glycoprotein , western blot , chondroitin sulfate , glycosaminoglycan , microbiology and biotechnology , biology , endoplasmic reticulum , extracellular matrix , gene , paleontology
Abstract Bikunin (Bkn) isoforms are serum chondroitin sulfate (CS) proteoglycans synthesized by the liver. They include two light forms, that is, the Bkn core protein and the Bkn linked to the CS chain (urinary trypsin inhibitor [UTI]), and two heavy forms, that is, pro‐α‐trypsin inhibitor and inter‐α‐trypsin inhibitor, corresponding to UTI esterified by one or two heavy chains glycoproteins, respectively. We previously showed that the Western‐blot analysis of the light forms could allow the fast and easy detection of patients with linkeropathy, deficient in enzymes involved in the synthesis of the initial common tetrasaccharide linker of glycosaminoglycans. Here, we analyzed all serum Bkn isoforms in a context of congenital disorders of glycosylation (CDG) and showed very specific abnormal patterns suggesting potential interests for their screening and diagnosis. In particular, genetic deficiencies in V‐ATPase (ATP6V0A2‐CDG, CCDC115‐CDG, ATP6AP1‐CDG), in Golgi manganese homeostasis (TMEM165‐CDG) and in the N ‐acetyl‐glucosamine Golgi transport (SLC35A3‐CDG) all share specific abnormal Bkn patterns. Furthermore, for each studied linkeropathy, we show that the light abnormal Bkn could be further in‐depth characterized by two‐dimensional electrophoresis. Moreover, besides being interesting as a specific biomarker of both CDG and linkeropathies, Bkn isoforms' analyses can provide new insights into the pathophysiology of the aforementioned diseases.