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Cardiovascular Genetics

Our research focuses on the identification of new genes and pathways involved in cardiovascular disorders, including aortic aneurysms, congenital heart defects and cardiomyopathies. Although individually rare, these disorders account for significant morbidity and mortality in both adults and children. The aim of our research is to better understand the underlying disease mechanisms and develop new strategies for therapeutic interventions.


Biventricular hypertrophy due to homozygous ALPK3 mutation (left) [Almomani et al, JACC 2016]. Aortic root aneurysm (middle) and aortic dissection (right) in patient with aneurysms-osteoarthritis syndrome [van de Laar et al, Nat Genet 2011].

In order to find new genes, we use several approaches including family-based linkage analysis, homozygosity mapping, whole exome sequencing and in silico prediction models. We are currently implementing expression profiling analysis in aortic tissues using RNA sequencing. Further in vitro and in vivo studies are performed at the zebrafish facility, the department of pathology, and with national and international collaborators.
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Pedigree of family with pediatric cardiomyopathy due to homozygous ALPK3 mutation (upper left) [Almomani et al, JACC 2016]. Linkage analysis in family with aortic aneurysms, SMAD3 mutation overview (lower left) and heterotrimeric complex of SMAD proteins (lower right) [van de Laar et al, Nat Genet 2011; van de Laar et al, J Med Genet 2012].

Besides finding new genes, we are also interested in studying the mutational and phenotypic spectra and genotype-phenotypic correlations of known disease genes. Furthermore, we actively participate in several national and international networks to improve the care for patients and families with inherited cardiovascular disorders.

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Hematoxylin and eosin staining showing focal hypertrophy of cardiomyocytes and subendocardial fibroelastosis (left) [Almomani et al, JACC 2016]. Electron microscopy (middle) and immunohistochemistry (right) analysis showing normal intercalated disc morphology [unpublished data].