FAMILIAL NON-SYNDROMIC CONOTRUNCAL DEFECTS ARE NOT ASSOCIATED WITH A 22Q11 MICRODELETION

Molecular studies have shown microdeletions in region q11 of chromosom e 22 in nearly all patients with DiGeorge, velocardiofacial and conotr uncal anomaly face syndromes (DGS, VCFS and CTAFS, respectively) and i n a high percentage of non-syndromic familial cases of conotruncal def ects (CTD). CTD account for roughly a fourth to a third of all non-syn dromic congenital heart defects (CHD), thus, 22q11 could harbor a majo r genetic factor of CHD. We searched for a 22q11 microdeletion in fami lial cases of non-syndromic CTD. Thirty-six cases of various isolated CTD, that is without history of hypocalcemia, immune deficiency, absen t thymus, and dysmorphic appearance, were selected. With 48F8, a cosmi d probe localized in the smallest deleted region of the DiGeorge criti cal region (DGCR), we found no deletions by fluorescence in situ hybri dization in these 36 affected individuals of 16 families with recurren t CTD. Moreover, D22S264, a microsatellilte localized at the distal pa rt of the largest deleted region? was used to genotype the patients. T hirty-two patients out of 37 were heterozygous and hence not deleted a t this locus, whereas 5 were uninformative. In conclusion, there are n o large deletions in familial cases of various CTD, whether these defe cts are identical or not within a family. This result does not rule ou t other minor anomalies in this chromosomal region.