A.V. Postma PhD

Research Associate
Main activities
Genetics of rare (congenital) diseases
Focus of research

My research aims to identify the underlying genetic cause(s) in rare (congenital) diseases. To this end I generate data, or employ existing datasets, using various state-of-the-art techniques such as linkage analysis, SNP-chip (GWAS), whole exome or genome sequencing, targeted sequencing, variant analysis and prediction, RNA-seq, pathway analyses, array CGH, and epigenetic techniques such as chip-seq, ATAC-seq, Hi-C etc. The right combination of these techniques and datasets can lead to the identification of the genetic background of rare diseases. My current resarch areas are:

1 Genetics of Congenital Heart Disease
Congenital heart disease (CHD) is the most common type of birth defect, accounting for one-third of all major congenital anomalies. Worldwide, 1.35 million infants are born with CHD each year. In the Netherlands, CHD occurs in 7 per 1000 live births. A broad phenotypic spectrum exists for CHDs. Conotruncal cardiac defects are among the most prevalent and severe. They are associated with severe late complications, requiring lifelong medical care. Tetralogy of Fallot (TOF, consisting of a ventricular septal defect, obstruction of the right ventricular outflow tract, override of the ventricular septum by the aortic root, and right ventricular hypertrophy) and Transposition of the Great Arteries (TGA, characterised by ventriculo-arterial discordance, where the pulmonary artery arises from a morphological left ventricle and the aorta arises from a morphological right ventricle), account for more than half of conotruncal cardiac defects and 5-10% of all CHDs. Although there have been tremendous advances in diagnosis and treatment of congenital heart disease (CHD), our knowledge of causes of CHD is very limited. Recent clinical and basic research has shown the importance of genetic factors in causation of CHD. The novel high-throughput DNA sequencing technologies that have lately become available (namely next-generation sequencing, NGS) are now expected to provide an important impetus for CHD gene discovery, even in cases with sporadic (non-familial) presentation. Some recent successful examples are the identification of a gain-of-function mutation in TBX5, a cardiac transcription factor, and its involvement in atrial fibrillation in the setting of Holt-Oram disease. Two GWAS studies on the common genetics of TOF and ASD type II and the identification of MYH7 mutations as a cause of Ebsteins anomaly, and TAB2 mutations in patients with outflow tract defects.
Current major focusses of our group for CHD genetics are:
• Transposition of the Great Arteries
• Tetralogy of Fallot
• Familial (consanguineous) CHD

2 Genetics of rare developmental syndromes/diseases
Congenital cardiac and neural tube defects account for 21 percent of late stage fetal or neonatal loss. Chromosomal aberrations commonly contributing to fetal demise are routinely identified via karyotype or comparative genome hybridization (CGH) array analysis; however, these techniques do not identify single nucleotide changes, thus many affected pregnancies remain without a genetic diagnosis. To understand what the genetic cause is for rare developmental syndromes/diseases we use traditional genetic methods such as linkage analysis or homozygosity analysis, coupled to whole exome or genome sequencing (WES/WGS) and other data sources in the hope to uncover the causal variant(s). Case in point, we were the first to describe a novel syndrome including sacral agenesis, abnormal ossification of the vertebral bodies and a persistent notochordal canal and to provide evidence that homozygous mutations in the T/Brachyury gene underlie this syndrome. Another recent success story was the linking of the SIRT6 gene, a chromatin-associated protein, to a syndrome involving perinatal loss of life due to a number of severe neurodevelopmental and cardiac anomalies.

Publications, google scholar

Peer-reviewer profile, publon

ORCID researcher ID

Key publications
  • Ellesøe Sabrina G., Workman Christopher T., Bouvagnet Patrice, Loffredo Christopher A., McBride Kim L., Hinton Robert B., van Engelen Klaartje, Gertsen Emma C., Mulder Barbara J. M., Postma Alex V., Anderson Robert H., Hjortdal Vibeke E., Brunak Søren, Larsen Lars A. Familial co-occurrence of congenital heart defects follows distinct patterns European heart journal 2018;39 (12):1015-1022 [PubMed]
  • Postma A. V., Alders M., Sylva M., Bilardo C. M., Pajkrt E., van Rijn R. R., Schulte-Merker S., Bulk S., Stefanovic S., Ilgun A., Barnett P., Mannens M. M. A. M., Moorman A. F. M., Oostra R. J., van Maarle M. C. Mutations in the T (brachyury) gene cause a novel syndrome consisting of sacral agenesis, abnormal ossification of the vertebral bodies and a persistent notochordal canal Journal of medical genetics 2014;51 (2):90-97 [PubMed]
  • Postma Alex V., van Engelen Klaartje, van de Meerakker Judith, Rahman Thahira, Probst Susanne, Baars Marieke J. H., Bauer Ulrike, Pickardt Thomas, Sperling Silke R., Berger Felix, Moorman Antoon F. M., Mulder Barbara J. M., Thierfelder Ludwig, Keavney Bernard, Goodship Judith, Klaassen Sabine Mutations in the Sarcomere Gene MYH7 in Ebstein Anomaly Circulation. Cardiovascular genetics 2011;4 (1):43-50 [PubMed]
  • Postma Alex V., van de Meerakker Judith B. A., Mathijssen Inge B., Barnett Phil, Christoffels Vincent M., Ilgun Aho, Lam Jan, Wilde Arthur A. M., Lekanne Deprez Ronald H., Moorman Antoon F. M. A gain-of-function TBX5 mutation is associated with atypical Holt-Oram syndrome and paroxysmal atrial fibrillation Circulation research 2008;102 (11):1433-1442 [PubMed]
All Publications
Research programmes

Prof. M.M.A.M. Mannens PhD (Genome diagnostics i.p. epigenetics of disease)

Prof. V.M. Christoffels PhD (Transcriptional mechanism controlling heart development, regeneration and rhythm)

A.V. Postma PhD (Promoties)