Asset Details
Do you wish to reserve the book?
B3GALT6 mutations lead to compromised connective tissue biomechanics in Ehlers-Danlos syndrome
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
B3GALT6 mutations lead to compromised connective tissue biomechanics in Ehlers-Danlos syndrome
Do you wish to request the book?
B3GALT6 mutations lead to compromised connective tissue biomechanics in Ehlers-Danlos syndrome
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
B3GALT6 mutations lead to compromised connective tissue biomechanics in Ehlers-Danlos syndrome
2025
Overview
Ehlers-Danlos syndromes (EDS) comprise a genetically and clinically heterogenous group of rare diseases that cause severe, often fatal, damage to connective tissue. The molecular basis of EDS implicates defects in extracellular matrix components, including various fibrillar collagens and glycosaminoglycans (GAGs). However, the precise pathogenic mechanisms behind EDS remain elusive. Here, we have implemented a multi-tiered approach to demonstrate the functional impact of B3GALT6 mutations on biochemical and developmental processes, ultimately leading to the spondylodysplastic subtype of EDS (spEDS), characterized by severe musculoskeletal symptoms. We show that the loss of function of β1,3-galactosyltransferase 6 (β3GalT6) is partially compensated by β1,3-glucuronosyltransferase 3 (GlcAT-I), the next enzyme in the GAG biosynthetic pathway. In addition, results from transcriptomics, collagen analysis, and biophysical experiments revealed that impaired collagen maturation, including defective glycosylation of collagen XII, contributes to altered tissue structure and biomechanics, the hallmarks of spEDS. Our findings unravel a new pathogenic mechanism of spEDS and bring us one step closer to therapeutic strategies, including cell and tissue engineering.
Publisher
American Society for Clinical Investigation,American Society for Clinical investigation
Subject
/ Collagen
/ Connective Tissue - metabolism
/ Connective Tissue - pathology
/ Connective Tissue - physiopathology
/ E coli
/ Ehlers-Danlos Syndrome - genetics
/ Ehlers-Danlos Syndrome - metabolism
/ Ehlers-Danlos Syndrome - pathology
/ Enzymes
/ Extracellular Matrix - metabolism
/ Female
/ Galactosyltransferases - genetics
/ Galactosyltransferases - metabolism
/ Genetics
/ Glycosaminoglycans - metabolism
/ Humans
/ Kinases
/ Male
/ Mutation
/ Patients
/ Proteins
