Genetic analysis of chromosome 22q11.2 markers in congenital heart disease.

Congenital heart disease (CHD) is a common cardiac defect found in infants and children. Despite advances in diagnosis and treatment, our understanding of the causative mechanism and etiology of CHD is limited. To determine the genetic etiology of CHD, we selected 11 consecutive short tandem-repeat polymorphic (STRP) markers located in the interval of the 22q11.2 region to perform genotype analysis on a large number of CHD patients (>120) and their normal relatives (>220). The results show that as regards the distribution of allelic size and frequency of these STRP markers, there were no significant differences between the CHD patients and the normal volunteers. This indicates that there is no linkage disequilibrium with these markers in CHD. In the level of heterozygosity for each marker in nonsyndromic CHD and conotruncal heart defect (CTD), there were no significant differences between the two populations. In syndromic CHD, the level of heterozygosity for D22S1648 was significantly lower than that observed in the unaffected population (chi(2) = 11.25; P = 0.001). This suggests that there may be a deletion at the D22S1648 locus, and the low heterozygosity of D22S1648 indicates that this marker can be used as a genetic marker for detecting microdeletions in 22q11.2. With the use of fluorescence in situ hybridization (FISH) and real-time quantitative polymerase chain reaction (PCR) performed on syndromic patients, we confirmed the molecular results.