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

ABSTRACT: Chromosome 4q deletion is one of the most frequently detected genomic imbalance events in congenital heart disease (CHD) patients. However, a portion of CHD-associated 4q deletions without known CHD genes suggests unknown CHD genes within these intervals. Here, we have shown that knockdown of SORBS2, a 4q interval gene, disrupted sarcomeric integrity of cardiomyocytes and caused reduced cardiomyocyte number in human embryonic stem cell differentiation model. Molecular analyses revealed decreased expression of second heart field (SHF) marker genes and impaired NOTCH and SHH signaling in SORBS2-knockdown cells. Exogenous SHH rescued SORBS2 knockdown-induced cardiomyocyte differentiation defects. Sorbs2^-/- mouse mutants had atrial septal hypoplasia/aplas

SUBMITTER: Liang F 

PROVIDER: S-EPMC8186900 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature