Molecular characterization of chromosome 22 deletions by short tandem repeat polymorphism (STRP) in patients with conotruncal heart defects

The haploinsufficiency of chromosome 22q11.2 can cause both DiGeorge and velocardiofacial syndromes, both of which are characterized by conotruncal heart defects as well as a wide range of other extracardiac anomalies. Several studies have demonstrated that approximately 10-20% of patients with conotruncal heart defects have a 22q11.2 deletion. In clinical laboratories, the deletion is usually detected by fluorescent in situ hybridization (FISH). We set up a polymerasse chain reaction-based non-radioactive method for molecular analysis of the 22q11.2 region in patients with conotruncal cardiac defects. Sixty-four children with conotruncal defects and their parents were genotyped by polymerase chain reaction, using fifteen polymorphic markers. We identified nine deletions (confirmed by FISH): eight were "de novo" and one familial, maternally inherited. Six deletion were paternal and three of maternal origin. There were seven deletions of 3 Mb and the other two were of 1.5 Mb. This method is a cost-effettive means of characterizing the 22q11.2 region and it can be applied for a rapid screening of 22q11.2 deletion in patients at risk. In agreement with previously published data, we found no correlation between the sizes and the parental origin of deletions and cardiac or extracardiac phenotypes.