PUBLICATION

A familial congenital heart disease with a possible multigenic origin involving a mutation in BMPR1A

Authors
Demal, T.J., Heise, M., Reiz, B., Dogra, D., Brænne, I., Reichenspurner, H., Männer, J., Aherrahrou, Z., Schunkert, H., Erdmann, J., Abdelilah-Seyfried, S.
ID
ZDB-PUB-190301-3
Date
2019
Source
Scientific Reports   9: 2959 (Journal)
Registered Authors
Abdelilah-Seyfried, Salim
Keywords
none
MeSH Terms
  • Adult
  • Animals
  • Bone Morphogenetic Protein Receptors, Type I/genetics*
  • Bone Morphogenetic Protein Receptors, Type I/metabolism
  • Disease Models, Animal
  • Endocardium/metabolism
  • Female
  • Genetic Linkage/genetics
  • Heart Defects, Congenital/genetics*
  • Humans
  • Male
  • Mutation/genetics
  • Zebrafish
PubMed
30814609 Full text @ Sci. Rep.
Abstract
The genetics of many congenital heart diseases (CHDs) can only unsatisfactorily be explained by known chromosomal or Mendelian syndromes. Here, we present sequencing data of a family with a potentially multigenic origin of CHD. Twelve of nineteen family members carry a familial mutation [NM_004329.2:c.1328 G > A (p.R443H)] which encodes a predicted deleterious variant of BMPR1A. This mutation co-segregates with a linkage region on chromosome 1 that associates with the emergence of severe CHDs including Ebstein's anomaly, atrioventricular septal defect, and others. We show that the continuous overexpression of the zebrafish homologous mutation bmpr1aap.R438H within endocardium causes a reduced AV valve area, a downregulation of Wnt/ß-catenin signalling at the AV canal, and growth of additional tissue mass in adult zebrafish hearts. This finding opens the possibility of testing genetic interactions between BMPR1A and other candidate genes within linkage region 1 which may provide a first step towards unravelling more complex genetic patterns in cardiovascular disease aetiology.
Genes / Markers
Figures
Figure Gallery
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes