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Impact of NAD deficiency on congenital heart disease

Victor Chang Cardiac Research Institute & University of New South Wales

  • Cardiovascular Senior Researcher Grant
Date Funded:
  • 6 October, 2021
Chief Investigator/s:
  • Professor Sally Dunwoodie

Project Summary

Reducing the impact of nictotinamide adenine dinucleotide (NAD) deficiency in causing congenital heart disease (CHD), extra-cardiac anomalies (ECA) and miscarriage.

What is the issue for NSW?

CHD is the most common type of malformation representing a third of the total and can occur with ECA. CHD also accounts for the most birth defect hospitalisations. CHD is caused by genetic and/or environmental factors. However, in 80% of cases the specific cause is unknown, leaving affected families with limited to no options to minimise recurrence. We discovered that mutations in genes required to make NAD cause NAD deficiency which results in CHD+ECA and miscarriage. In mice, NAD deficiency is prevented by vitamin B3. However, we currently do not know how common lowered NAD levels are in women and during pregnancy, and if it leads to CHD+ECA and miscarriage, and if so which form of vitamin B3 would best treat NAD deficiency.

What does the research aim to do and how?

We will quantify NAD in women to determine what the normal levels of NAD are and if levels are affected by pregnancy. We will then look for a link between low NAD and adverse pregnancy outcomes such as CHD+/-ECA and miscarriage.

We will quantify the function of NAD genes from CHD patients that carry a DNA change to identify which of these are causing this birth defect, using yeast and enzyme assays.

We will determine the best type of vitamin B3 to raise NAD levels to prevent adverse pregnancy outcomes, using mice.