Figure 1.

Cardiovascular phenotype enrichment groups. The stacked bar chart represents the total number of samples used for TBX1 resequencing (Cohort). The number in each group is also indicated above the bar chart (Cohort). Those with a significant intracardiac or aortic arch malformation are referred to as having a congenital heart defect (CHD). Total samples of isolated individual malformations were shown on the top of the figure (Isolate). For example, the total number of patients with atrial septal defects (ASDs) is 80. Among the 80, 16 had an ASD but no other defects (not shown in the table). The rest had ASD as well as other cardiovascular defects. TBX1 sequencing was performed on 48 ASD patients, while genotyping for common SNP variants was performed in all of them. The number 32 derives from subtracting 48 from 80. There were 385, 22q11DS subjects with VSDs (ventricular septal defects; 52 samples with VSD only). VSD occurs as part of tetralogy of Fallot (TOF) and persistent truncus arteriosus (PTA). Among those in the VSD enrichment group, 150 had a VSD that was not associated with TOF or PTA (52 samples had VSD but no other intracardiac defect). A separate designation was made for those with a VSD but not in association with TOF or PTA (VSD2). There were 150 with VSD as the only intracardiac defect. A total of 181 patients had TOF; 75 were subjected to TBX1 resequencing and all were genotyped. Sixty 22q11DS patients had TOF but no aortic arch defect or ASD (not shown in the table). Pulmonic stenosis (PS) occurs in association with TOF and it can co-occur with a VSD. In some of the echocardiogram summaries, PS and VSD were indicated but TOF wasn’t. In those situations, we did not assume the patient had a TOF. A total of 124 comprised the PS enrichment group (pulmonic atresia or stenosis). Sixty were subjected to TBX1 resequencing and all were genotyped. Among those with PS, only 4 had this malformation and no other intracardiac or aortic arch anomaly. Only 28 of 55 had a PTA but no other anomaly. Fifty-four patients had an interrupted aortic arch type B (IAAB); 34 were sequenced and all were genotyped. Only 4 total had an IAAB but no other intracardiac or aortic arch defect. A total of 137 had a right-sided aortic arch (RAA) and 77 were subjected to TBX1 resequencing, while all were genotyped. Thirty-three patients had RAA as the only cardiovascular defect. In total, 664 patients had an intracardiac and/or aortic arch malformation (CHD; cases) and were genotyped while 231 were subjected to TBX1 resequencing. A total of 358 patients had no detectable CHD (controls), and 112 were sequenced, while all were genotyped. Defects such as small patent foramen ovale or abnormal branching of the subclavian arteries were not always detected or noted and were not included in the analysis.