| Autor: |
Syx, Delfien, Damme, Tim, Symoens, Sofie, Maiburg, Merel C., Laar, Ingrid, Morton, Jenny, Suri, Mohnish, Del Campo, Miguel, Hausser, Ingrid, Hermanns‐Lê, Trinh, Paepe, Anne, Malfait, Fransiska |
| Zdroj: |
Human Mutation; May2015, Vol. 36 Issue 5, p535-547, 13p |
| Abstrakt: |
ABSTRACT Bi-allelic variants in CHST14, encoding dermatan 4- O-sulfotransferase-1 (D4ST1), cause musculocontractural Ehlers-Danlos syndrome (MC-EDS), a recessive disorder characterized by connective tissue fragility, craniofacial abnormalities, congenital contractures, and developmental anomalies. Recently, the identification of bi-allelic variants in DSE, encoding dermatan sulfate epimerase-1 (DS-epi1), in a child with MC-EDS features, suggested locus heterogeneity for this condition. DS-epi1 and D4ST1 are crucial for biosynthesis of dermatan sulfate (DS) moieties in the hybrid chondroitin sulfate (CS)/DS glycosaminoglycans (GAGs). Here, we report four novel families with severe MC-EDS caused by unique homozygous CHST14 variants and the second family with a homozygous DSE missense variant, presenting a somewhat milder MC-EDS phenotype. The glycanation of the dermal DS proteoglycan decorin is impaired in fibroblasts from D4ST1- as well as DS-epi1-deficient patients. However, in D4ST1-deficiency, the decorin GAG is completely replaced by CS, whereas in DS-epi1-deficiency, still some DS moieties are present. The multisystemic abnormalities observed in our patients support a tight spatiotemporal control of the balance between CS and DS, which is crucial for multiple processes including cell differentiation, organ development, cell migration, coagulation, and connective tissue integrity. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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