Congenital heart defects appear in greater frequency among relatives of patients with heart defects. Patients with DiGeorge syndrome (DGS) and velocardiofacial syndrome (VCFS) have an increased frequency of heart defects. A majority of DGS and VCFS patients, and many sporadic and familial patients with conotruncal heart defects, manifest deletions within a distinct region of chromosome 22q11.
To characterize molecular-genetic changes in the 22q11 region of patients with conotruncal and non-conotruncal heart defects we evaluated 35 patients, 21 with Tetralogy of Fallot (TOF) and 14 with other right ventricular defects (non TOF). DNA was isolated from tissues removed at corrective heart surgery and analyzed by PCR and gel electrophoresis for homo – or heterozygosity of 9 markers of polymorphic short tandem repeats (STRs) along the 22q11 region. DNA isolated from the blood of 45 health individuals represented the general population (GP). Of the 21 TOF patients, 5 were homozygous for 2, 5 for 3, 1 for 3, 1 for 5, and 2 for 8 consecutive markers. Six of the 14 non-TOF patients were homozygous for 2 consecutive markers.
The frequency of heterozygocity of each marker is summarized in the table:| Marker | 420 | 1638 | 1648 | 941 | 944 | COMT | 264 | 311 | 278 |
| TOF | 0.91 | 0.81 | 0.29b | 0.43a | 0.33b | 0.57 | 0.81 | 0.76 | 0.81 |
| Non-TOF | 0.93 | 0.86 | 0.50 | 0.79 | 0.50 | 0.71 | 0.79 | 0.93 | 0.79 |
| GP | 0.77 | 0.89 | 0.53 | 0.68 | 0.68 | 0.52 | 0.88c | 0.74c | 0.78c |
These findings support an association between congenital heart defects and deletions in 22p11, indicating a specific region between markers D22S1638 and COMT. Namely, distal to the locus of the frequently studied N25/D22S75 FISH (fluorescence in situ hybridization) market.
Our study demonstrates the usefulness of STR polymorphism in characterizing genetic alterations in congenital heart defects and suggests a specific region that may harbor TOF susceptibility genes.
