Format

Send to

Choose Destination
See comment in PubMed Commons below
J Med Genet. 2004 Sep;41(9):684-90.

Somatic NKX2-5 mutations as a novel mechanism of disease in complex congenital heart disease.

Author information

  • 1Drug Research and Medical Biotechnology, Fraunhofer Institute of Toxicology and Experimental Medicine, Nikolai-Fuchs-Strasse 1, D-30625 Hanover, Germany.

Abstract

NKX2-5 is a pivotal transcription factor in heart development. Previous studies on lymphocytic DNA provided evidence of familial NKX2-5 gene mutations in cardiac malformations. Common mutations are rare in unrelated families. We analysed, by direct sequencing, the gene encoding NKX2-5 in the diseased heart tissues of 68 patients with complex congenital heart disease, focussing particularly on atrial, ventricular, and atrioventricular septal defects. We identified 35 non-synonymous NKX2-5 mutations in the diseased heart tissues of patients. These mutations were mainly absent in normal, for example, unaffected, heart tissue of the same patient, indicating the somatic nature and mosaicism of mutations. We also observed multiple mutations and multiple haplotypes, as well as mutations in Down's syndrome patients with cardiac malformations. Taken collectively, the above results suggest the somatic nature of NKX2-5 mutations associated with complex cardiac malformations. Somatic mutations in transcription factor genes of cardiac progenitor cells provide a novel mechanism of disease.

Comment in

PMID:
15342699
PMCID:
PMC1735891
DOI:
10.1136/jmg.2003.017483
[PubMed - indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Support Center