CRELDl: A Possible Genetic Risk Factor for Truncus Arteriosus

Abstract Congenital heart malformations affect approximately 1% of live births, 10% of stillbirths, and 20 % of spontaneous abortions (Robinson et al 2003, Schleiffarth, 2007). Anomalies of the outflow tract account for one third of congenital heart disease cases (Schleiffarth, 2007). Truncus arteriosus (TA) is a major cardiac outflow tract defect and is highly lethal with about 50% of those born with this anomaly dying in the first month of life (Sinzobahhamvia, 2008). We are interested in the potential role for CRELD1 in the pathogenesis of TA based on the observation of poor endocardial cushion development in the outflow tract of a CRELD1 knockout mouse. TA is the failure of outflow tract septation and is therefore a logical phenotype to be associated with CRELD1 deficiency. The main question underlying this thesis is whether or not people with TA have mutated CRELD1 genes. Exons 5, 6, 7, 8, 9, and 10 of CRELD1 were sequenced in 26 TA patients. Electropherograms were observed using mutation analysis software. Four irregularities were found in exon 5. The most significant of these findings is the possible addition of thymine, which results in a “stop” codon change that truncates translation of the CRELD1 protein. The potential of CRELD1 as a genetic risk factor for TA remains a possibility. Investigation of the sequencing irregularities in exon 5 are significant avenues of further research