Molecular characterization of tetralogy of Fallot with 22q11 microdeletion

Background. Chromosome 22q11 deletion has been implicated in a number of conotruncal congenital heart defects, including tetralogy of Fallot (TF). The effect of the chromosome deletion on the spectrum of TF and the parental origin of the deleted chromosome have been determined here. Methods and Results. Sixty patients with sporadic TF were analyzed for deletion at 22p11 by genotype analysis using five microsatellite markets: D22S427, D22S944, D22S264 and D22S311, and by quantitative PCR. Deletion of chromosome 22q11 was identified in 10 patients (16.6%). When the type of TF was divided into two categories as TF with pulmonary atresia (TF/PA; 15 patients) and TF with pulmonary stenosis (TF/PS; 45 patients), about 33% (5/15) of the patients having TF/PA and 11% (5/45) of the patients having TF/PS had deleted chromosomes 22. Parental origin of the deleted chromosomes could be determined in nine patients, with two of patenal and seven of maternal origin. There was no correlation between the size of the deletion, cardiac manifestation and paternal origin. Conclusions. Biased parental origin was found in the syndromic TF with del22q11. There appears to be preferential occurrence of maternal deletion in sporadic cases. The most common mode of transmission in patients of TF with del22q11 is de novo, without parental hemizygosity (> 90%). Autosomal dominant heredity in TF with del22q11 is relatively uncommon (< 10%).