| Experiment Id | GSE77798 | Name | Pathogenesis of Hypoplastic Left Heart Syndrome [RNA-seq] |
| Experiment Type | RNA-Seq | Study Type | WT vs. Mutant |
| Source | GEO | Curation Date | 2022-04-28 |
| description | Congenital heart disease (CHD) is a prevalent birth defect affecting up to 1% of live births. While a genetic etiology is indicated by increased recurrence risk and association with chromosomal abnormalities, the genetics of CHD is poorly understood and likely complex. Here we show hypoplastic left heart syndrome (HLHS), a severe CHD with high morbidity/mortality, has a multigenic etiology. Analysis of 8 HLHS mutant mouse lines recovered from a large-scale mutagenesis screen showed no mutations are shared in common. In the *Ohia* mouse line, mutations in 2 genes, *Pcdha9*/*Sap130*, act synergistically to cause HLHS. Cardiomyocyte proliferation and differentiation defects likely act in concert with valve abnormalities to cause HLHS. Network analysis of mutations recovered in HLHS mice and 68 HLHS patients point to Notch signaling disruption, a pathway previously implicated in HLHS. These findings demonstrate large-scale mutagenesis is an effective systems approach for interrogating the complex genetics of human diseases. Expression profiling using RNA-seq of 16 samples collected from both left ventricle (LV) and right ventricle (RV) of HLHS mice (n=1 for E13.5, E14.5 and E17.5) and their littermate controls (n=1 for E13.5, and n=2 for E14.5 and E17.5 each). |
