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The purpose of this study was to determine whether the levels of heterozygosity and microdeletion of specific loci within the DiGeorge critical region (del22q11) are associated with different phenotypes of tetralogy of Fallot (TF). Examinations were conducted on 84 sporadic TF patients and their unaffected parents for del22q11, using the following 9 simple tandem repeat polymorphic microsatellite markers: D22S420, D22S427, D22S941, D22S944, D22S264, D22S311, D22S425, D22S303, D22S257. The microdeletions were confirmed using quantitative PCR with markers TUPLE1, exon 2 of the UFD1L gene, and D22S264; the boundaries of these microdeletions were estimated using genotypic analyses of the unaffected family members. The del22q11 was identified in 14 patients (16.6%). The boundary of the shortest region of deletion overlap (SRO) in these 14 TF patients was identified, proximally using D22S427 and distally using the TUPLE 1 gene. The deletion of exon 2 of the UFD1L gene and TUPLE1 gene was identified in 13 patients (13/14 cases; 93%). The SRO in TF patients with del22q11 was at or close to the ADU breakpoint and centromeric to the UFD1L gene. The level of heterozygosity for the marker D22S944 in TF patients without del22q11 (n = 70) was found to be significantly lower than expected. Overall, this study demonstrated the significantly low level of heterozygosity within DiGeorge critical region in TF patients with or without del22q11. Our results suggest that the genetic factors leading to DiGeorge/velocardiofacial syndrome might also be partly responsible for TF phenotypes.

Monozygotic twins with chromosome 22q11 microdeletions offer an ideal situation to observe the association of microdeletion and disrupted cardiovascular patterning. We report monozygotic twins concordant for 22q11.2 microdeletion but discordant for cardiovascular patterning. Both twins showed identical intracardiac defects including tetralogy of Fallot with pulmonary atresia. Nevertheless, their great vessel patternings were variable. These twins show that the mispatterning of the great vessels may not correlate with intracardiac morphogenesis. The discordant development of the great vessels, especially in the pulmonary vascular system, has clinical significance for prognosis. The phenotypic variability of cardiovascular anomalies seen in 22q11 microdeletion cannot be explained on the basis of genotypic difference.