Gerodermia osteodysplastica is an autosomal recessive disorder characterized by wrinkly skin and osteoporosis. Here we demonstrate that gerodermia osteodysplastica is caused by loss-of-function mutations in SCYL1BP1, which is highly expressed in skin and osteoblasts. The protein localizes to the Golgi apparatus and interacts with Rab6, identifying SCYL1BP1 as a golgin. These results associate abnormalities of the secretory pathway with age-related changes in connective tissues.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3122266 | PMC |
| http://dx.doi.org/10.1038/ng.252 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Targeting TGF-β signaling, oxidative stress, and cellular senescence rescues osteoporosis in gerodermia osteodysplastica.
Aging Cell
December 2024
Institut für Medizinische Genetik Und Humangenetik, Charité-Universitätsmedizin Berlin, Berlin, Germany.
GORAB is a key regulator of Golgi vesicle transport and protein glycanation. Loss of GORAB function in gerodermia osteodysplastica (GO) causes shortening of glycosaminoglycan chains, leading to extracellular matrix disorganization that results in wrinkled skin, osteoporosis and elevated TGF-β signaling. In this study, we investigated the role of TGF-β-signaling, oxidative stress, and resulting cellular senescence in the osteoporosis phenotype of GO.
View Article and Find Full Text PDFFurther Defining the Phenotypic Spectrum of B3GAT3 Mutations and Literature Review on Linkeropathy Syndromes.
Genes (Basel)
August 2019
Division of Biology and Genetics, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy.
The term linkeropathies (LKs) refers to a group of rare heritable connective tissue disorders, characterized by a variable degree of short stature, skeletal dysplasia, joint laxity, cutaneous anomalies, dysmorphism, heart malformation, and developmental delay. The LK genes encode for enzymes that add glycosaminoglycan chains onto proteoglycans via a common tetrasaccharide linker region. Biallelic variants in XYLT1 and XYLT2, encoding xylosyltransferases, are associated with Desbuquois dysplasia type 2 and spondylo-ocular syndrome, respectively.
View Article and Find Full Text PDFGORAB scaffolds COPI at the trans-Golgi for efficient enzyme recycling and correct protein glycosylation.
Nat Commun
January 2019
School of Biology, Faculty of Biology, Medicine and Health, University of Manchester, The Michael Smith Building, Oxford Road, Manchester, M13 9PT, UK.
Article Synopsis
- - COPI is essential for protein transport in cells, mainly recruited by Arf GTPases to form transport intermediates for proteins like Golgi enzymes.
- - The study identifies GORAB, a protein linked to gerodermia osteodysplastica, as a key player in the COPI machinery, aiding in its recruitment to the trans-Golgi network through interactions with Scyl1.
- - Mutations in GORAB disrupt its function and disrupt the retrieval process for Golgi enzymes, leading to issues in glycosylation, which contributes to the disease's development.
Impaired proteoglycan glycosylation, elevated TGF-β signaling, and abnormal osteoblast differentiation as the basis for bone fragility in a mouse model for gerodermia osteodysplastica.
PLoS Genet
March 2018
Institut für Medizinische Genetik und Humangenetik, Charité -Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Gerodermia osteodysplastica (GO) is characterized by skin laxity and early-onset osteoporosis. GORAB, the responsible disease gene, encodes a small Golgi protein of poorly characterized function. To circumvent neonatal lethality of the GorabNull full knockout, Gorab was conditionally inactivated in mesenchymal progenitor cells (Prx1-cre), pre-osteoblasts (Runx2-cre), and late osteoblasts/osteocytes (Dmp1-cre), respectively.
View Article and Find Full Text PDFGeroderma osteodysplasticum: Histological features and the role of panel-based exome sequencing in diagnosis.
Ultrastruct Pathol
August 2018
a Yorkshire Regional Genetics Service , Chapel Allerton Hospital, Leeds Teaching Hospitals NHS Trust, Leeds , UK.
Geroderma osteodysplasticum (GO) has clinical and histological features that overlap with other causes of wrinkly skin. Here we present the case of a child diagnosed with GO following exome sequencing of a panel of genes covering the wide differential diagnosis. The histological features of the overlapping conditions are presented, highlighting the utility of panel testing for conditions of this type.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!