SORBS2 is a genetic factor contributing to cardiac malformation of 4q deletion syndrome patients

• DOI: 10.7554/elife.67481
• Publication Date: 2021-06-08T00:17:13Z
• Authors: Fei Liang; Bo Wang; Juan Geng; Guoling You; Jingjing Fa; Min Zhang; Hunying Sun; Huiwen Chen; Qihua Fu; Xiaoqing Zhang; Zhen Zhang
• Keywords: Haploinsufficiency; Pathogenesis; GATA4

Chromosome 4q deletion is one of the most frequently detected genomic imbalance events in congenital heart disease (CHD) patients. However, a portion CHD-associated deletions without known CHD genes suggests unknown within these intervals. Here, we have shown that knockdown SORBS2 , interval gene, disrupted sarcomeric integrity cardiomyocytes and caused reduced cardiomyocyte number human embryonic stem cell differentiation model. Molecular analyses revealed decreased expression second field (SHF) marker impaired NOTCH SHH signaling SORBS2- cells. Exogenous rescued knockdown-induced defects. Sorbs2 -/- mouse mutants had atrial septal hypoplasia/aplasia or double septum (DAS) derived from posterior SHF with similar alteration. Rare variants were significantly enriched cohort 300 Our findings indicate regulator development its contribute to pathogenesis. The presence DAS hearts reveals first molecular etiology this rare anomaly linked paradoxical thromboembolism.