Research lab: Michael E. Mitchell, MD,
and Aoy Tomita-Mitchell, PhD
Lead investigators:
Research in Cardiothoracic Surgery includes the genetic and molecular etiology of congenital heart disease. We are interested in identifying genetic risk factors of heart malformations and in understanding how these genetic alterations lead to clinical variability and impact pathways at the molecular level. Ultimately, we hope to be able to improve immediate and long-term outcomes for patients with congenital heart disease. To reach this goal, our lab is focused on the following:
- Patient recruitment to a congenital heart disease tissue and DNA bank, a repository of DNA and surgical discards from patients with congenital heart disease.
- Development and utilization of high-throughput genetic technologies in order to reduce the high costs of performing large scale genetic studies.
- Integration of genetic information with clinical variability and outcomes.
Collaborating investigators:
- John E. Baker, PhD
- Daniel Beard
- David Bick, MD
- Ulrich Broeckel, MD
- Stephen Duncan
- Mindy Dwinell
- Michael Earing, MD
- Andrew Greene
- Martin Hessner, PhD
- Howard J. Jacob, PhD
- Michael Kron
- Joe Lazar
- John Lough
- Carol Moreno-Quinn
- Kathleen A. Mussatto, PhD, RN
- Michael Olivier
- Andrew Pelech, MD
- Ramani Ramchandran, PhD
- Elena Semina, PhD
- Craig Struble, Marquette University
- James Tweddell, MD
- Tetsuro Wakatsuki
Development of genetic screening assays for congenital heart disease. DiGeorge syndrome type 1 is estimated to be the most prevalent inheritable genetic deletion syndrome, occurring in 1 per 4,000 live births. A large range of clinical characteristics characterizes this autosomal dominant disease, including congenital heart defects, velopharyngeal abnormalities, learning difficulties, endocrine abnormalities, renal anomalies and immune defects. Unfortunately, the diagnosis of DiGeorge syndrome is delayed in most individuals because of this varying clinical phenotype, as well as the fact that the diagnostic cytogenetic fluorescent in situ hybridization probe misses at least 15 percent of all microdeletions in the DGS1 region (chromosome 22q11.2). As a result, it is estimated that only 25 percent of DGS1 patients are diagnosed in infancy, with the median age of diagnosis for all other DGS1 patients being 8 years of age. Early diagnosis and appropriate medical intervention can prevent and effectively treat many of the co-morbidities associated with DGS1. There is a critical need to develop a more sensitive and cost-effective screening method for DGS1. We strongly believe that by detecting DGS1 subjects early in life, it will allow for potentially life-saving medical interventions for the many disabilities, such as congenital heart disease and severe immunodeficiency.
Collaborating investigators:
Development of a non-invasive diagnostic test for fetal genetic and chromosomal abnormalities. An increasing number of fetal medical conditions can be successfully managed during the neonatal period if an early diagnosis is made. Because of the inadequate sensitivity and specificity of currently available non-invasive tools, amniocentesis and chorionic villus sampling, both invasive procedures, remain the standard for the definitive detection of fetal genetic and chromosomal abnormalities. Both of these procedures carry health risk for the developing fetus. We are developing a non-invasive approach using maternal plasma to identify fetal genetic variation associated with congenital heart disease. We believe that early intervention, including immediate postnatal access to cardiac care, will improve neonatal mortality rates and long-term outcomes for Wisconsin's children.
Collaborating investigators:
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