Familial non-syndromic conotruncal defects are not associated with a 22q11 microdeletion.

Molecular studies have shown microdeletions in region q11 of chromosome 22 in nearly all patients with DiGeorge, velocardiofacial and conotruncal anomaly face syndromes (DGS, VCFS and CTAFS, respectively) and in a high percentage of non-syndromic familial cases of conotruncal defects (CTD). CTD account for roughly a fourth to a third of all non-syndromic congenital heart defects (CHD), thus, 22q11 could harbor a major genetic factor of CHD. We searched for a 22q11 microdeletion in familial cases of non-syndromic CTD. Thirty-six cases of various isolated CTD, that is without history of hypocalcemia, immune deficiency, absent thymus, and dysmorphic appearance, were selected. With 48F8, a cosmid probe localized in the smallest deleted region of the DiGeorge critical region (DGCR), we found no deletions by fluorescence in situ hybridization in these 36 affected individuals of 16 families with recurrent CTD. Moreover, D22S264, a microsatellite localized at the distal part of the largest deleted region, was used to genotype the patients. Thirty-two patients out of 37 were heterozygous and hence not deleted at this locus, whereas 5 were uninformative. In conclusion, there are no large deletions in familial cases of various CTD, whether these defects are identical or not within a family. This result does not rule out other minor anomalies in this chromosomal region.