{"controller"=>"catalog", "action"=>"show", "id"=>"247018822"}
  • EN
  • DA

Danish NationalResearch Database

  • Search Publications & Researchers
  • Open Access Indicator
  • Publications
  • Researchers
Example Finds records
water{} containing the word "water".
water supplies"{}" containing the phrase "water supplies".
author:"Doe, John"author:"{}" containing the prase "Doe, John" in the author field.
title:IEEEtitle:{} containing the word "IEEE" in the title field.
Need more help? Advanced search tutorial
  • Selected (0)
  • History

Characterization of a novel missense mutation in the prodomain of GDF5, which underlies brachydactyly type C and mild Grebe type chondrodysplasia in a large Pakistani family

    • Save to Mendeley
    • Export to BibTeX
    • Export to RIS
    • Email citation
Authors:
  • Farooq, Muhammad ;
    Close
    Medical Genetics Program, Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, Københavns Universitet
  • Nakai, Hiroyuki ;
    Close
    unknown
  • Fujimoto, Atsushi ;
    Close
    unknown
  • Fujikawa, Hiroki ;
    Close
    unknown
  • Kjaer, Klaus Wilbrandt ;
    Close
    Medical Genetics Program, Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, Københavns Universitet
  • Baig, Shahid Mahmood ;
    Close
    unknown
  • Shimomura, Yutaka
    Close
    unknown
DOI:
10.1007/s00439-013-1330-3
Abstract:
All TGF-beta family members have a prodomain that is important for secretion. Lack of secretion of a TGF-beta family member GDF5 is known to underlie some skeletal abnormalities, such as brachydactyly type C that is characterized by a huge and unexplained phenotypic variability. To search for potential phenotypic modifiers regulating secretion of GDF5, we compared cells overexpressing wild type (Wt) GDF5 and GDF5 with a novel mutation in the prodomain identified in a large Pakistani family with Brachydactyly type C and mild Grebe type chondrodyslplasia (c527T>C; p.Leu176Pro). Initial in vitro expression studies revealed that the p.Leu176Pro mutant (Mut) GDF5 was not secreted outside the cells. We subsequently showed that GDF5 was capable of forming a complex with latent transforming growth factor binding proteins, LTBP1 and LTBP2. Furthermore, secretion of LTBP1 and LTBP2 was severely impaired in cells expressing the Mut-GDF5 compared to Wt-GDF5. Finally, we demonstrated that secretion of Wt-GDF5 was inhibited by the Mut-GDF5, but only when LTBP (LTBP1 or LTBP2) was co-expressed. Based on these findings, we suggest a novel model, where the dosage of secretory co-factors or stabilizing proteins like LTBP1 and LTBP2 in the microenvironment may affect the extent of GDF5 secretion and thereby function as modifiers in phenotypes caused by GDF5 mutations.
Type:
Journal article
Language:
English
Published in:
Human Genetics, 2013, Vol 132, Issue 11, p. 1253-1264
Main Research Area:
Medical science
Publication Status:
Published
Review type:
Peer Review
Submission year:
2013
Scientific Level:
Scientific
ID:
247018822

Full text access

  • Doi Get publisher edition via DOI resolver
Checking for on-site access...

On-site access

At institution

  • Copenhagen university.en

Metrics

Feedback

Sitemap

  • Search
    • Statistics
    • Tutorial
    • Data
    • FAQ
    • Contact
  • Open Access
    • Overview
    • Development
    • FAQ
    • Contact
  • About
    • Institutions
    • Release History
    • Cookies and privacy policy

Copyright © 1998–2018.

Fivu en