Genetic Mapping of the 22q11.2 Deletion Syndrome (DiGeorge Syndrome) Microdeletion Types Revealed Novel Candidate Breakpoints

Background: 22q11.2 deletion syndrome (DiGeorge Syndrome) is a rare disorder that involves a de novo hemizygous microdeletion within the 22q11.2 chromosomal locus. Individuals affected by this condition display a wide array of clinical phenotypes as well as haplotype sequences, which render understanding the genotype–phenotype relationship quite difficult. Additionally, the complex structure of the 22q11.2 low-copy repeats (LCRs), which usually inhibits sequencing efforts, has complicated the study of possible breakpoints that instigate the deletion events. In this study, 22q11.2 deletion syndrome is investigated on a genomic and phenotypic level for the purpose of determining the impact of each deletion type and identifying possible candidate breakpoints. Methods: In the present study, a systematic review combined with a secondary genomic analysis has been executed following PRISMA guidelines using PubMed and Scopus publications in order to estimate its holistic genomic map, genomic functional elements, and key genomic regions such as LCRs. A statistical content analysis of the affected chromosomal regions was also performed. Groups of functional elements with common traits were composed, and their contribution to the deletion events was investigated. Finally, the 22q11.2 repeat regions were screened for palindromic AT-rich repeats. Results: Of the 8202 unique publications studied in this work, only 65 met the inclusion criteria. The estimated genomic map of 22q11.2 deletion syndrome in the secondary genomic analysis revealed 11 distinct microdeletions occurring between eight LCRs, and a new repeat region within the CES region (CESRR), of which the LCR22A-LCR22D deletion was the most frequently reported. Last but not least, the palindromic analyses indicated eight critical groups as candidate breakpoints that potentially form four distinct patterns, and ten palindromic AT-rich repeat (PATRR) regions were identified amongst LCR22A, LCR22B, LCR22D, LCR22F and LCR22H. Conclusions: The study results validate the differentiating clinical contribution between the proximal and the distal segments. Eight novel candidate breakpoints and five new PATRRs were identified that require further study to establish their involvement in 22q11.2 microdeletion events.