TBX20 loss-of-function mutation contributes to double outlet right ventricle.

摘要: Congenital heart disease (CHD), the most prevalent birth defect in humans worldwide, is still a leading non‑infectious cause of infant morbidity and mortality. Increasing evidence demonstrates that genetic risk factors play key role pathogenesis CHD, more than 50 genes have been linked to various types CHD. Nevertheless, CHD heterogeneous disorder components underpinning an overwhelming majority cases remain unknown. In present study, entire coding exons flanking introns TBX20 gene, which codes for T-box transcription factor essential proper development heart, were sequenced cohort 146 unrelated patients with The available relatives index patient harboring identified mutation 200 ethnically matched healthy individuals used as controls also genotyped TBX20. functional characteristics assayed by using dual-luciferase reporter assay system. As result, novel heterozygous mutation, p.R143W, was double outlet right ventricle (DORV). Genetic analyses pedigree proband revealed family, co-segregated DORV transmitted autosomal dominant pattern complete penetrance. missense absent 400 control chromosomes altered amino acid completely conserved evolutionarily across species. Functional analysis mutant had significantly diminished transcriptional activity compared its wild-type counterpart. To best our knowledge, this study first report association loss-of-function increased susceptibility humans, provides insight into molecular mechanisms responsible suggesting potential implications antenatal prophylaxis