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dc.contributor.author
Lim, Pei Jin
dc.contributor.author
Lindert, Uschi
dc.contributor.author
Opitz, Lennart
dc.contributor.author
Hausser, Ingrid
dc.contributor.author
Rohrbach, Marianne
dc.contributor.author
Giunta, Cecilia
dc.date.accessioned
2019-08-16T07:50:31Z
dc.date.available
2019-08-16T02:19:28Z
dc.date.available
2019-08-16T07:50:31Z
dc.date.issued
2019-07
dc.identifier.other
10.3390/genes10070517
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/358951
dc.identifier.doi
10.3929/ethz-b-000358951
dc.description.abstract
Kyphoscoliotic Ehlers–Danlos Syndrome (kEDS) is a rare genetic heterogeneous disease clinically characterized by congenital muscle hypotonia, kyphoscoliosis, and joint hypermobility. kEDS is caused by biallelic pathogenic variants in either PLOD1 or FKBP14. PLOD1 encodes the lysyl hydroxylase 1 enzyme responsible for hydroxylating lysyl residues in the collagen helix, which undergo glycosylation and form crosslinks in the extracellular matrix thus contributing to collagen fibril strength. FKBP14 encodes a peptidyl-prolyl cis–trans isomerase that catalyzes collagen folding and acts as a chaperone for types III, VI, and X collagen. Despite genetic heterogeneity, affected patients with mutations in either PLOD1 or FKBP14 are clinically indistinguishable. We aim to better understand the pathomechanism of kEDS to characterize distinguishing and overlapping molecular features underlying PLOD1-kEDS and FKBP14-kEDS, and to identify novel molecular targets that may expand treatment strategies. Transcriptome profiling by RNA sequencing of patient-derived skin fibroblasts revealed differential expression of genes encoding extracellular matrix components that are unique between PLOD1-kEDS and FKBP14-kEDS. Furthermore, we identified genes involved in inner ear development, vascular remodeling, endoplasmic reticulum (ER) stress, and protein trafficking that were differentially expressed in patient fibroblasts compared to controls. Overall, our study presents the first transcriptomics data in kEDS revealing distinct molecular features between PLOD1-kEDS and FKBP14-kEDS, and serves as a tool to better understand the disease.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
MDPI
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject
kyphoscoliotic Ehlers-Danlos Syndrome
en_US
dc.subject
EDS type VI
en_US
dc.subject
transcriptomics
en_US
dc.subject
connective tissue
en_US
dc.subject
extracellular matrix
en_US
dc.subject
PLOD1
en_US
dc.subject
FKBP14
en_US
dc.title
Transcriptome Profiling of Primary Skin Fibroblasts Reveal Distinct Molecular Features Between PLOD1- and FKBP14-Kyphoscoliotic Ehlers–Danlos Syndrome
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
dc.date.published
2019-07-08
ethz.journal.title
Genes
ethz.journal.volume
10
en_US
ethz.journal.issue
7
en_US
ethz.pages.start
517
en_US
ethz.size
18 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.publication.place
Basel
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00003 - Schulleitung und Dienste::00022 - Bereich VP Forschung / Domain VP Research::02207 - Functional Genomics Center Zurich / Functional Genomics Center Zurich
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00003 - Schulleitung und Dienste::00022 - Bereich VP Forschung / Domain VP Research::02207 - Functional Genomics Center Zurich / Functional Genomics Center Zurich
ethz.date.deposited
2019-08-16T02:19:32Z
ethz.source
WOS
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2019-08-16T07:50:53Z
ethz.rosetta.lastUpdated
2021-02-15T05:39:49Z
ethz.rosetta.versionExported
true
ethz.COinS
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