English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  A new subtype of brachydactyly type B caused by point mutations in the bone morphogenetic protein antagonist NOGGIN.

Lehmann, K., Seemann, P., Silan, F., Goecke, T. O., Irgang, M., Kjaer, K. W., et al. (2007). A new subtype of brachydactyly type B caused by point mutations in the bone morphogenetic protein antagonist NOGGIN. The American Journal of Human Genetics: AJHG, 81(12), 388-396. doi:10.1086/519697.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-8193-8 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-8194-6
Genre: Journal Article
Alternative Title : Am. J. Hum. Genet.

Files

show Files
hide Files
:
PIIS000292970761204X.pdf (Any fulltext), 505KB
 
File Permalink:
-
Name:
PIIS000292970761204X.pdf
Description:
-
Visibility:
Restricted (Max Planck Institute for Molecular Genetics, MBMG; )
MIME-Type / Checksum:
application/pdf
Technical Metadata:
Copyright Date:
-
Copyright Info:
eDoc_access: INSTITUT
License:
-

Locators

show

Creators

show
hide
 Creators:
Lehmann, K., Author
Seemann, Petra1, Author              
Silan, F., Author
Goecke, T. O., Author
Irgang, Markus2, Author
Kjaer, K. W., Author
Kjaergaard, S., Author
Mahoney, M. J., Author
Morlot, S., Author
Reissner, C., Author
Kerr, B., Author
Wilkie, A. O. M., Author
Mundlos, Stefan1, Author              
Affiliations:
1Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433557              
2Max Planck Society, ou_persistent13              

Content

show
hide
Free keywords: -
 Abstract: Brachydactyly type B (BDB) is characterized by terminal deficiency of fingers and toes, which is caused by heterozygous truncating mutations in the receptor tyrosine kinase–like orphan receptor 2 (ROR2) in the majority of patients. In a subset of ROR2-negative patients with BDB, clinically defined by the additional occurrence of proximal symphalangism and carpal synostosis, we identified six different point mutations (P35A, P35S, A36P, E48K, R167G, and P187S) in the bone morphogenetic protein (BMP) antagonist NOGGIN (NOG). In contrast to previously described loss-of-function mutations in NOG, which are known to cause a range of conditions associated with abnormal joint formation but without BDB, the newly identified BDB mutations do not indicate a major loss of function, as suggested by calculation of free-binding energy of the modeled NOG-GDF5 complex and functional analysis of the micromass culture system. Rather, they presumably alter NOG’s ability to bind to BMPs and growth-differentiation factors (GDFs) in a subtle way, thus disturbing the intricate balance of BMP signaling. The combined features observed in this phenotypic subtype of BDB argue for a functional connection between BMP and ROR2 signaling and support previous findings of a modulating effect of ROR2 on the BMP-receptor pathway through the formation of a heteromeric complex of the receptors at the cell surface.

Details

show
hide
Language(s): eng - English
 Dates: 2007-08-01
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: -
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: The American Journal of Human Genetics : AJHG
  Alternative Title : Am. J. Hum. Genet.
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 81 (12) Sequence Number: - Start / End Page: 388 - 396 Identifier: ISSN: 0002-9297