English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Novel missense mutations (p.T596M and p.P1797H) in NOTCH1 in patients with bicuspid aortic valve

Mohamed, S. A., Aherrahrou, Z., Liptau, H., Erasmi, A. W., Hagemann, C., Wrobel, S., et al. (2006). Novel missense mutations (p.T596M and p.P1797H) in NOTCH1 in patients with bicuspid aortic valve. Biochemical and Biophysical Research Communications, 354(4), 1460-1465. doi:10.1016/j.bbrc.2006.05.046.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-83F0-8 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-83F1-6
Genre: Journal Article
Alternative Title : Biochem Biophys Res Commun

Files

show Files
hide Files
:
sdarticle.pdf (Any fulltext), 194KB
 
File Permalink:
-
Name:
sdarticle.pdf
Description:
-
Visibility:
Restricted (Max Planck Institute for Molecular Genetics, Berlin; )
MIME-Type / Checksum:
application/pdf
Technical Metadata:
Copyright Date:
-
Copyright Info:
eDoc_access: MPG
License:
-

Locators

show

Creators

show
hide
 Creators:
Mohamed, Salah A., Author
Aherrahrou, Zouhair, Author
Liptau, Henrike, Author
Erasmi, Armin W., Author
Hagemann, Carolin, Author
Wrobel, Sandra, Author
Borzym, Katja1, Author              
Schunkert, Heribert, Author
Sievers, Hans H., Author
Erdmann, Jeanette, Author
Affiliations:
1Mechanisms of Transcriptional Regulation (Sebastiaan H. Meijsing), Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479641              

Content

show
hide
Free keywords: NOTCH1; Bicuspid aortic valve; Valve calcification; Missense mutations
 Abstract: The bicuspid aortic valve (BAV) is the most common congenital cardiac malformation, occurring in 1–2% of the population. In a recent report, mutations in NOTCH1 a signaling and transcriptional regulator have been shown to cause BAV in two families. This study provides data on systematic sequencing in search for novel mutations in NOTCH1 gene in a large sample BAV. For the first time, we report results of a systematic mutation-analysis based on DNA-sequencing of all coding exons and adjacent splice consensus sequences of NOTCH1 gene. Our analyses revealed 57 NOTCH1 sequence variants. Twenty-one variants are located within exons and 36 within intronic or 5′-UTR sequences. Thirty-five variants were described previously as polymorphisms. The remaining 22, however, were neither listed in public SNP databases nor in the literature and were therefore considered novel. Seventeen variants were found only once (MAF = 1%), of these 15 were novel. Two sequence variants led to amino acid substitutions (p.T596M and p.P1797H) and are located in highly conserved regions of the NOTCH1 protein. In addition, these two mutations could not be detected in at least 327 healthy controls by using RFLP-analysis. The functional relevance of the other 13 novel and rare variants could not be proven without further functional examination. In this study, we provide a new evidence that the mutations in the NOTCH1 gene may trigger the underlying mechanism causing the valve calcification, especially in BAV. In conclusion, NOTCH1 gene mutations do not only play a role in familiar BAV, but can also be observed in approximately 4% of sporadic cases.

Details

show
hide
Language(s): eng - English
 Dates: 2006-07-14
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: -
 Identifiers: eDoc: 305124
DOI: 10.1016/j.bbrc.2006.05.046
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Biochemical and Biophysical Research Communications
  Alternative Title : Biochem Biophys Res Commun
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 354 (4) Sequence Number: - Start / End Page: 1460 - 1465 Identifier: ISSN: 0006-291x