Introduction and objectives: Ventricular septal defect (VSD) is one of the major forms of congenital heart disease (CHD) in individuals with Homo sapiens chromosome 22q11 (HSA22q11) deletion syndrome. The objective was to identify candidate genes associated with VSD located within HSA22q11 by analyzing loss of heterozygosity (LOH) using microsatellite genotyping and by gene dosage analysis in seven candidate genes.
Methods: The study involved 82 families with CHD, which included 261 individuals (85 patients and 176 siblings and parents). All were screened for LOH in the HSA22q11 region by microsatellite (n=10) genotyping. Bioinformatic strategies were used to characterize seven candidate genes located within this region in greater detail. Quantitative polymerase chain reaction analysis was used to determine the dosages of the seven candidate genes in 16 patients with LOH of HSA22q11.
Results: Overall, 42 out of 85 patients (49.4%) with CHD had at least one LOH in the HSA22q11 region. Moreover, LOH of HSA22q11 was found in 17 out of 29 patients with a VSD and in three out of four families with two offspring affected by CHD. Dosage analysis of the seven candidate genes showed recurrent heterozygous deletion of HIRA, GNB1L and TUBA8 genes in 16 VSD patients with a LOH of HSA22q11.
Conclusions: Microsatellite genotyping identified LOH of HSA22q11 in several types of CHD. Heterozygous deletion of HIRA, GNB1L or TUBA8 genes might play an important role in ventricular septum development. Since CHD can be a familial disease, screening the siblings of a proband for LOH of HSA22q could be valuable for early diagnosis and treatment.