PTPN11 and pulmonary arterial hypertension: As mentioned previously, three de novo variants were identified in PAH risk gene TBX4 and one variant each in CHD risk genes NOTCH1 and PTPN11. However, testing for enrichment of all rare de novo variants in PAH-CHD trio probands compared to an estimated background mutation rate indicated no overall enrichment, likely due to the small sample size.