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Identifying genetic and epigenetic factors associated with congenital heart disease in people with Down syndrome.

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Lay summary

Down syndrome (trisomy 21) is the commonest chromosomal condition worldwide and it occurs in 1 in 377 births in the United Kingdom (NCARDRS Congenital Anomaly Official Statistics Report, 2020). One of the major complications of having a baby with Down syndrome (DS) is that 40-50% of them are born with congenital heart disease (CHD) (Santoro and Seffensen, 2021). This prevalence corresponds to 100-fold increase in people with DS compared to the general population (NCARDRS Report, 2020).

Currently, prenatal screening includes screening for trisomy 13,18,21. Unlike trisomy 13 and 18, trisomy 21 is compatible with human survival and majority of babies born with T21 survive beyond infancy period and many live into adulthood with a relatively good quality of life (www.dsmig.org.uk). CHD however, remains the leading cause of death from birth anomalies worldwide and it is the leading cause of morbidity and mortality in individuals with DS (Dimopoulos, 2023). For expectant parents receiving results of screening, accurate, current prognostic data are crucial so they could weigh the options when deciding about their pregnancy wether to proceed or terminate. Additional information about the likelihood of CHD could help better guide their decision making process. This could potentially be the future of perinatal genetic screening for T21.

This project will analyse variants within the DS critical region (DSCR) located in chromosome 21. Pelleri et al. 2017 found that this narrowed region within chromosome 21 is a critical region that is associated with DS and CHD when 3 copies of it is present. Although the DSCR accounts for features of DS, only 40-50% of those with the DSCR has CHD.

This project aims to find the genetic and epigenetic factors within the region that influence the development of CHD in people with DS.

Reference:
1. NACRDRS Report 2020: https://digital.nhs.uk/data-and-information/publications/statistical/ncardrs-congenital-anomaly-statistics-annual-data/ncardrs-congenital-anomaly-statistics-report-2020
2. Santoro, S.L. and Steffensen, E.H., 2021. Congenital heart disease in Down syndrome–A review of temporal changes. Journal of Congenital Cardiology, 5, pp.1-14.
3. Dimopoulos, K., Constantine, A., Clift, P., Condliffe, R., Moledina, S., Jansen, K., Inuzuka, R., Veldtman, G.R., Cua, C.L., Tay, E.L.W. and Opotowsky, A.R., 2023. Cardiovascular complications of down syndrome: scoping review and expert consensus. Circulation, 147(5), pp.425-441.
4. Pelleri, M.C., Gennari, E., Locatelli, C., Piovesan, A., Caracausi, M., Antonaros, F., Rocca, A., Donati, C.M., Conti, L., Strippoli, P. and Seri, M., 2017. Genotype-phenotype correlation for congenital heart disease in Down syndrome through analysis of partial trisomy 21 cases. Genomics, 109(5-6), pp.391-400.

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