Insulin-like growth factor binding proteins (IGFBPs) play important physiological functions through the modulation of IGF signaling as well as IGF-independent mechanisms. Despite the established role of IGFs in development, a similar role for the seven known IGFBPs has not been established in humans. Here, we show that an autosomal-recessive syndrome that consists of progressive retinal arterial macroaneurysms and supravalvular pulmonic stenosis is caused by mutation of IGFBP7. Consistent with the recently established inhibitory role of IGFBP7 on BRAF signaling, the BRAF/MEK/ERK pathway is upregulated in these patients, which may explain why the cardiac phenotype overlaps with other disorders characterized by germline mutations in this pathway. The retinal phenotype appears to be mediated by a role in vascular endothelium, where IGFBP7 is highly expressed.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3155176 | PMC |
| http://dx.doi.org/10.1016/j.ajhg.2011.07.010 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Increased A-to-I RNA editing in atherosclerosis and cardiomyopathies.
PLoS Comput Biol
April 2023
Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel.
Adenosine-to-inosine RNA editing is essential to prevent undesired immune activation. This diverse process alters the genetic content of the RNA and may recode proteins, change splice sites and miRNA targets, and mimic genomic mutations. Recent studies have associated or implicated aberrant editing with pathological conditions, including cancer, autoimmune diseases, and neurological and psychiatric conditions.
View Article and Find Full Text PDFHepatic Transcriptome Analysis Reveals Genes, Polymorphisms, and Molecules Related to Lamb Tenderness.
Animals (Basel)
February 2023
Department of Animal Production and Technology, Faculty of Animal Science, IPB University, Bogor 16680, Indonesia.
Tenderness is a key meat quality trait that determines the public acceptance of lamb consumption, so genetic improvement toward lamb with higher tenderness is pivotal for a sustainable sheep industry. However, unravelling the genomics controlling the tenderness is the first step. Therefore, this study aimed to identify the transcriptome signatures and polymorphisms related to divergent lamb tenderness using RNA deep sequencing.
View Article and Find Full Text PDFSingle-cell RNA sequencing identifies -expressing osteocytes in response to 1,25-dihydroxyvitamin D treatment.
Front Physiol
January 2023
Department of Molecular Endocrinology, Fujii Memorial Institute of Medical Sciences, Institute of Advanced Medical Sciences, Tokushima University, Tokushima, Japan.
Fibroblast growth factor 23 (FGF23), a hormone, mainly produced by osteocytes, regulates phosphate and vitamin D metabolism. By contrast, 1,25-dihydroxyvitamin D, the active form of vitamin D, has been shown to enhance FGF23 production. While it is likely that osteocytes are heterogenous in terms of gene expression profiles, specific subpopulations of -expressing osteocytes have not been identified.
View Article and Find Full Text PDFIsolation of a novel missense mutation in insulin receptor as a spontaneous revertant in ImpL2 mutants in Drosophila.
Development
January 2023
Laboratory for Growth Control Signaling, RIKEN Center for Biosystems Dynamics Research (BDR), Kobe, Hyogo 650-0047, Japan.
Evolutionarily conserved insulin/insulin-like growth factor (IGF) signaling (IIS) correlates nutrient levels to metabolism and growth, thereby playing crucial roles in development and adult fitness. In the fruit fly Drosophila, ImpL2, an ortholog of IGFBP7, binds to and inhibits the function of Drosophila insulin-like peptides. In this study, we isolated a temperature-sensitive mutation in the insulin receptor (InR) gene as a spontaneous revertant in ImpL2 null mutants.
View Article and Find Full Text PDFCOG4 mutation in Saul-Wilson syndrome selectively affects secretion of proteins involved in chondrogenesis in chondrocyte-like cells.
Front Cell Dev Biol
October 2022
Human Genetics Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, United States.
Saul-Wilson syndrome is a rare skeletal dysplasia caused by a heterozygous mutation in COG4 (p.G516R). Our previous study showed that this mutation affected glycosylation of proteoglycans and disturbed chondrocyte elongation and intercalation in zebrafish embryos expressing the COG4 variant.
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!