{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T11:01:13Z","timestamp":1771844473516,"version":"3.50.1"},"reference-count":89,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,22]],"date-time":"2026-02-22T00:00:00Z","timestamp":1771718400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>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\u2013phenotype 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.<\/jats:p>","DOI":"10.3390\/genes17020248","type":"journal-article","created":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T10:00:52Z","timestamp":1771840852000},"page":"248","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetic Mapping of the 22q11.2 Deletion Syndrome (DiGeorge Syndrome) Microdeletion Types Revealed Novel Candidate Breakpoints"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9577-9923","authenticated-orcid":false,"given":"Louis","family":"Papageorgiou","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, University of West Attica, Agioy Spyridonos 28, 12243 Egaleo, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Nikolopoulou","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics, Department of Biotechnology, Agricultural University of Athens, 11855 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6294-1988","authenticated-orcid":false,"given":"Eleni","family":"Koniari","sequence":"additional","affiliation":[{"name":"University Research Institute of Maternal and Child Health and Precision Medicine, School of Medicine, National Kapodistrian University of Athens, 11527 Athens, Greece"},{"name":"Clinical and Translational Research Endocrine Unit, School of Medicine, National Kapodistrian University of Athens, 11528 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1469-1928","authenticated-orcid":false,"given":"Kyriaki","family":"Hatziagapiou","sequence":"additional","affiliation":[{"name":"University Research Institute of Maternal and Child Health and Precision Medicine, School of Medicine, National Kapodistrian University of Athens, 11527 Athens, Greece"},{"name":"Clinical and Translational Research Endocrine Unit, School of Medicine, National Kapodistrian University of Athens, 11528 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2313-1305","authenticated-orcid":false,"given":"Dimitrios","family":"Chaniotis","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of West Attica, Agioy Spyridonos 28, 12243 Egaleo, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5639-0528","authenticated-orcid":false,"given":"Apostolos","family":"Beloukas","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of West Attica, Agioy Spyridonos 28, 12243 Egaleo, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3098-5264","authenticated-orcid":false,"given":"George P.","family":"Chrousos","sequence":"additional","affiliation":[{"name":"University Research Institute of Maternal and Child Health and Precision Medicine, School of Medicine, National Kapodistrian University of Athens, 11527 Athens, Greece"},{"name":"Clinical and Translational Research Endocrine Unit, School of Medicine, National Kapodistrian University of Athens, 11528 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0919-0571","authenticated-orcid":false,"given":"Elias","family":"Eliopoulos","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics, Department of Biotechnology, Agricultural University of Athens, 11855 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6894-0774","authenticated-orcid":false,"given":"Trias","family":"Thireou","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics, Department of Biotechnology, Agricultural University of Athens, 11855 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1159\/000263173","article-title":"The syndrome of the congenitally shortened velum. The dual innervation of the soft palate","volume":"19","author":"Sedlackova","year":"1967","journal-title":"Folia Phoniatr."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1097\/00125817-200101000-00002","article-title":"The 22q11.2 deletion: From diversity to a single gene theory","volume":"3","author":"Lawrenson","year":"2001","journal-title":"Genet. Med."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Jameson, J.L. (1998). The 22q11 Deletion. Principles of Molecular Medicine, Humana Press.","DOI":"10.1007\/978-1-59259-726-0"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1016\/S0022-3476(65)81796-6","article-title":"A new concept of the cellular basis of immunity","volume":"67","author":"Cooper","year":"1965","journal-title":"J. Pediatr."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"32","DOI":"10.2214\/ajr.103.1.32","article-title":"Congenital absence of the thymus","volume":"103","author":"Kirkpatrick","year":"1968","journal-title":"Am. J. Roentgenol. Radium Ther. Nucl. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1016\/S0022-3476(68)80241-0","article-title":"Familial syndrome of right-sided aortic arch, mental deficiency, and facial dysmorphism","volume":"73","author":"Strong","year":"1968","journal-title":"J. Pediatr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1136\/adc.44.233.69","article-title":"Cardiofacial syndrome. Congenital heart disease and facial weakness, a hitherto unrecognized association","volume":"44","author":"Cayler","year":"1969","journal-title":"Arch. Dis. Child."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1080\/19315860902756136","article-title":"Velo-Cardio-Facial Syndrome","volume":"2","author":"Gothelf","year":"2009","journal-title":"J. Ment. Health Res. Intellect. Disabil."},{"key":"ref_9","first-page":"56","article-title":"A new syndrome involving cleft palate, cardiac anomalies, typical facies, and learning disabilities: Velo-cardio-facial syndrome","volume":"15","author":"Shprintzen","year":"1978","journal-title":"Cleft Palate J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1007\/BF00278938","article-title":"A deletion in chromosome 22 can cause DiGeorge syndrome","volume":"57","author":"Herva","year":"1981","journal-title":"Hum. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1136\/jmg.30.10.852","article-title":"DiGeorge syndrome: Part of CATCH 22","volume":"30","author":"Wilson","year":"1993","journal-title":"J. Med. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.jpeds.2005.03.007","article-title":"Defining the clinical spectrum of deletion 22q11.2","volume":"147","author":"Robin","year":"2005","journal-title":"J. Pediatr."},{"key":"ref_13","unstructured":"Cortes-Martin, J., Penuela, N.L., Sanchez-Garcia, J.C., Montiel-Troya, M., Diaz-Rodriguez, L., and Rodriguez-Blanque, R. (2022). Deletion Syndrome 22q11.2: A Systematic Review. Children, 9."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1007\/s10875-022-01418-y","article-title":"Clinical Practice Guidelines for the Immunological Management of Chromosome 22q11.2 Deletion Syndrome and Other Defects in Thymic Development","volume":"43","author":"Mustillo","year":"2023","journal-title":"J. Clin. Immunol."},{"key":"ref_15","unstructured":"Lackey, A.E., and Muzio, M.R. (2025). DiGeorge Syndrome. StatPearls, Treasure Island (FL) Ineligible Companies."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1186\/s13023-019-1170-x","article-title":"Association between phenotype and deletion size in 22q11.2 microdeletion syndrome: Systematic review and meta-analysis","volume":"14","author":"Rozas","year":"2019","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_17","first-page":"924","article-title":"A genetic etiology for DiGeorge syndrome: Consistent deletions and microdeletions of 22q11","volume":"50","author":"Driscoll","year":"1992","journal-title":"Am. J. Hum. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1007\/BF01972889","article-title":"Clinical and molecular study of DiGeorge sequence","volume":"153","author":"Wernert","year":"1994","journal-title":"Eur. J. Pediatr."},{"key":"ref_19","unstructured":"Chamarthi, V.S., Lackey, A.E., and Chamarthi, S. (2025). DiGeorge Syndrome. StatPearls, Treasure Island (FL) with Ineligible Companies."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/s11882-023-01071-4","article-title":"Chromosome 22q11.2 Deletion (DiGeorge Syndrome): Immunologic Features, Diagnosis, and Management","volume":"23","author":"Biggs","year":"2023","journal-title":"Curr. Allergy Asthma Rep."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Davies, E.G. (2013). Immunodeficiency in DiGeorge Syndrome and Options for Treating Cases with Complete Athymia. Front. Immunol., 4.","DOI":"10.3389\/fimmu.2013.00322"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Vervoort, L., and Vermeesch, J.R. (2022). The 22q11.2 Low Copy Repeats. Genes, 13.","DOI":"10.3390\/genes13112101"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1101\/gr.248682.119","article-title":"The 22q11 low copy repeats are characterized by unprecedented size and structural variability","volume":"29","author":"Demaerel","year":"2019","journal-title":"Genome Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1159\/000438708","article-title":"22q11.21 Deletion Syndromes: A Review of Proximal, Central, and Distal Deletions and Their Associated Features","volume":"146","author":"Burnside","year":"2015","journal-title":"Cytogenet. Genome Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1002\/pd.4823","article-title":"False positive cell free DNA screening for microdeletions due to non-pathogenic copy number variants","volume":"36","author":"Mather","year":"2016","journal-title":"Prenat. Diagn"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Sahajpal, N.S., Barseghyan, H., Kolhe, R., Hastie, A., and Chaubey, A. (2021). Optical Genome Mapping as a Next-Generation Cytogenomic Tool for Detection of Structural and Copy Number Variations for Prenatal Genomic Analyses. Genes, 12.","DOI":"10.1101\/2021.02.19.21251714"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Zormpa, T., Thireou, T., Beloukas, A., Chaniotis, D., Golfinopoulou, R., Vlachakis, D., Eliopoulos, E., and Papageorgiou, L. (2025). The Genetic Background of Ankylosing Spondylitis Reveals a Distinct Overlap with Autoimmune Diseases: A Systematic Review. J. Clin. Med., 14.","DOI":"10.3390\/jcm14113677"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Papageorgiou, L., Zervou, M.I., Vlachakis, D., Matalliotakis, M., Matalliotakis, I., Spandidos, D.A., Goulielmos, G.N., and Eliopoulos, E. (2021). Demetra Application: An integrated genotype analysis web server for clinical genomics in endometriosis. Int. J. Mol. Med., 47.","DOI":"10.3892\/ijmm.2021.4948"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1186\/s13643-021-01626-4","article-title":"The PRISMA 2020 statement: An updated guideline for reporting systematic reviews","volume":"10","author":"Page","year":"2021","journal-title":"Syst. Rev."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Gavril, E.C., Popescu, R., Nuca, I., Ciobanu, C.G., Butnariu, L.I., Rusu, C., and Panzaru, M.C. (2022). Different Types of Deletions Created by Low-Copy Repeats Sequences Location in 22q11.2 Deletion Syndrome: Genotype-Phenotype Correlation. Genes., 13.","DOI":"10.3390\/genes13112083"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Zodanu, G.K.E., Oszlanczi, M., Havasi, K., Kalapos, A., Racz, G., Katona, M., Ujfalusi, A., Nagy, O., Szell, M., and Nagy, D. (2021). Systemic Screening for 22q11.2 Copy Number Variations in Hungarian Pediatric and Adult Patients With Congenital Heart Diseases Identified Rare Pathogenic Patterns in the Region. Front. Genet., 12.","DOI":"10.3389\/fgene.2021.635480"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Funato, N. (2022). Craniofacial Phenotypes and Genetics of DiGeorge Syndrome. J. Dev. Biol., 10.","DOI":"10.3390\/jdb10020018"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2070","DOI":"10.1002\/ajmg.a.40504","article-title":"Molecular genetics of 22q11.2 deletion syndrome","volume":"176","author":"Morrow","year":"2018","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Du, Q., de la Morena, M.T., and van Oers, N.S.C. (2019). The Genetics and Epigenetics of 22q11.2 Deletion Syndrome. Front. Genet., 10.","DOI":"10.3389\/fgene.2019.01365"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1159\/000334262","article-title":"22q11.2 Distal Deletion Syndrome: Description of a New Case with Truncus Arteriosus Type 2 and Review","volume":"2","author":"Garavelli","year":"2011","journal-title":"Mol. Syndromol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1038\/ejhg.2015.219","article-title":"A French multicenter study of over 700 patients with 22q11 deletions diagnosed using FISH or aCGH","volume":"24","author":"Poirsier","year":"2016","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1664","DOI":"10.1038\/mp.2017.161","article-title":"A neurogenetic model for the study of schizophrenia spectrum disorders: The International 22q11.2 Deletion Syndrome Brain Behavior Consortium","volume":"22","author":"Gur","year":"2017","journal-title":"Mol. Psychiatry"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"40031","DOI":"10.1038\/srep40031","article-title":"An exploratory study of predisposing genetic factors for DiGeorge\/velocardiofacial syndrome","volume":"7","author":"Verges","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Torres-Juan, L., Rosell, J., Sanchez-de-la-Torre, M., Fibla, J., and Heine-Suner, D. (2007). Analysis of meiotic recombination in 22q11.2, a region that frequently undergoes deletions and duplications. BMC Med. Genet., 8.","DOI":"10.1186\/1471-2350-8-14"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/j.ejmg.2013.07.002","article-title":"Atypical copy number abnormalities in 22q11.2 region: Report of three cases","volume":"56","author":"Molck","year":"2013","journal-title":"Eur. J. Med. Genet."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e00507","DOI":"10.1002\/mgg3.507","article-title":"Atypical nested 22q11.2 duplications between LCR22B and LCR22D are associated with neurodevelopmental phenotypes including autism spectrum disorder with incomplete penetrance","volume":"7","author":"Woodward","year":"2019","journal-title":"Mol. Genet. Genom. Med."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Smyk, M., Geremek, M., Ziemkiewicz, K., Gambin, T., Kutkowska-Kazmierczak, A., Kowalczyk, K., Plaskota, I., Wisniowiecka-Kowalnik, B., Bartnik-Glaska, M., and Niemiec, M. (2023). Coexisting Conditions Modifying Phenotypes of Patients with 22q11.2 Deletion Syndrome. Genes, 14.","DOI":"10.3390\/genes14030680"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.ygeno.2005.10.002","article-title":"Computational analysis and refinement of sequence structure on chromosome 22q11.2 region: Application to the development of quantitative real-time PCR assay for clinical diagnosis","volume":"87","author":"Chen","year":"2006","journal-title":"Genomics"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1111\/j.1399-0004.2008.01008.x","article-title":"Concurrent microdeletion and duplication of 22q11.2","volume":"74","author":"Blennow","year":"2008","journal-title":"Clin. Genet."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Bertini, V., Azzara, A., Legitimo, A., Milone, R., Battini, R., Consolini, R., and Valetto, A. (2017). Deletion Extents Are Not the Cause of Clinical Variability in 22q11.2 Deletion Syndrome: Does the Interaction between DGCR8 and miRNA-CNVs Play a Major Role?. Front. Genet., 8.","DOI":"10.3389\/fgene.2017.00047"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1002\/ajmg.a.31662","article-title":"Detection of single clone deletions using array CGH: Identification of submicroscopic deletions in the 22q11.2 deletion syndrome as a model system","volume":"143A","author":"Tokuyasu","year":"2007","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1056\/NEJMoa0806544","article-title":"Genetic compensation in a human genomic disorder","volume":"360","author":"Rudolf","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1086\/340363","article-title":"Genomic disorders on 22q11","volume":"70","author":"McDermid","year":"2002","journal-title":"Am. J. Hum. Genet."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Liu, X., Gao, H., He, R., and Zhao, Y. (2021). Identifying of 22q11.2 variations in Chinese patients with development delay. BMC Med. Genom., 14.","DOI":"10.1186\/s12920-020-00849-z"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s11689-019-9267-z","article-title":"In the line-up: Deleted genes associated with DiGeorge\/22q11.2 deletion syndrome: Are they all suspects?","volume":"11","author":"Motahari","year":"2019","journal-title":"J. Neurodev. Disord."},{"key":"ref_51","first-page":"836","article-title":"Maternal cell-free DNA-based screening for fetal microdeletion and the importance of careful diagnostic follow-up","volume":"17","author":"Yatsenko","year":"2015","journal-title":"Genet. Med. Off. J. Am. Coll. Med. Genet."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1002\/ddrr.3","article-title":"Molecular mechanisms and diagnosis of chromosome 22q11.2 rearrangements","volume":"14","author":"Emanuel","year":"2008","journal-title":"Dev. Disabil. Res. Rev."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"12235","DOI":"10.1038\/s41598-020-69134-4","article-title":"Optical mapping of the 22q11.2DS region reveals complex repeat structures and preferred locations for non-allelic homologous recombination (NAHR)","volume":"10","author":"Pastor","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.tjog.2014.04.021","article-title":"Prenatal diagnosis and molecular cytogenetic characterization of chromosome 22q11.2 deletion syndrome associated with congenital heart defects","volume":"53","author":"Kuo","year":"2014","journal-title":"Taiwan. J. Obstet. Gynecol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.tjog.2015.12.014","article-title":"Prenatal diagnosis of 22q11.2 deletion syndrome associated with right aortic arch, left ductus arteriosus, cardiomegaly, and pericardial effusion","volume":"55","author":"Chen","year":"2016","journal-title":"Taiwan. J. Obstet. Gynecol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.biopsych.2013.07.019","article-title":"The 22q11.2 deletion syndrome as a window into complex neuropsychiatric disorders over the lifespan","volume":"75","author":"Jonas","year":"2014","journal-title":"Biol. Psychiatry"},{"key":"ref_57","first-page":"92","article-title":"The recurrent distal 22q11.2 microdeletions are often de novo and do not represent a single clinical entity: A proposed categorization system","volume":"16","author":"Mikhail","year":"2014","journal-title":"Genet. Med. Off. J. Am. Coll. Med. Genet."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1126\/science.abj6987","article-title":"The complete sequence of a human genome","volume":"376","author":"Nurk","year":"2022","journal-title":"Science"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"D862","DOI":"10.1093\/nar\/gkv1222","article-title":"ClinVar: Public archive of interpretations of clinically relevant variants","volume":"44","author":"Landrum","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e6","DOI":"10.1017\/S0016672317000040","article-title":"Analysis of pathogenic variants from the ClinVar database in healthy people using next-generation sequencing","volume":"99","author":"Rancelis","year":"2017","journal-title":"Genet. Res."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Papageorgiou, L., Papa, L., Papakonstantinou, E., Mataragka, A., Dragoumani, K., Chaniotis, D., Beloukas, A., Iliopoulos, C., Bongcam-Rudloff, E., and Chrousos, G.P. (2024). SNP and Structural Study of the Notch Superfamily Provides Insights and Novel Pharmacological Targets against the CADASIL Syndrome and Neurodegenerative Diseases. Genes, 15.","DOI":"10.3390\/genes15050529"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"6131","DOI":"10.1073\/pnas.1318948111","article-title":"Defining functional DNA elements in the human genome","volume":"111","author":"Kellis","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1007\/s00439-001-0615-0","article-title":"The HUGO Gene Nomenclature Committee (HGNC)","volume":"109","author":"Povey","year":"2001","journal-title":"Hum. Genet."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Delihas, N. (2020). Formation of human long intergenic non-coding RNA genes, pseudogenes, and protein genes: Ancestral sequences are key players. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0230236"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"3872","DOI":"10.1093\/hmg\/ddaa251","article-title":"Double strand breaks (DSBs) as indicators of genomic instability in PATRR-mediated translocations","volume":"29","author":"Lilley","year":"2021","journal-title":"Hum. Mol. Genet."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1016\/j.bbrc.2016.09.015","article-title":"Palindrome analyser\u2014A new web-based server for predicting and evaluating inverted repeats in nucleotide sequences","volume":"478","author":"Brazda","year":"2016","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Henn, L., Sievers, A., Hausmann, M., and Hildenbrand, G. (2023). Specific Patterns in Correlations of Super-Short Tandem Repeats (SSTRs) with G+C Content, Genic and Intergenic Regions, and Retrotransposons on All Human Chromosomes. Genes, 15.","DOI":"10.3390\/genes15010033"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.gde.2012.02.004","article-title":"Chromosomal translocations and palindromic AT-rich repeats","volume":"22","author":"Kato","year":"2012","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1038\/s41439-020-00127-5","article-title":"A reference catalog of DNA palindromes in the human genome and their variations in 1000 Genomes","volume":"7","author":"Ganapathiraju","year":"2020","journal-title":"Hum. Genome Var."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Inagaki, H., Kato, T., Tsutsumi, M., Ouchi, Y., Ohye, T., and Kurahashi, H. (2016). Palindrome-Mediated Translocations in Humans: A New Mechanistic Model for Gross Chromosomal Rearrangements. Front. Genet., 7.","DOI":"10.3389\/fgene.2016.00125"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"4447","DOI":"10.1073\/pnas.1101219108","article-title":"Deficiency of Dgcr8, a gene disrupted by the 22q11.2 microdeletion, results in altered short-term plasticity in the prefrontal cortex","volume":"108","author":"Fenelon","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Boz, V., Di Rosa, M., Pin, A., De Martino, E., Faletra, F., Baldo, F., Magnolato, A., and Valencic, E. (2025). From DGCR8 expression analysis to diseased pathways in 22q11.2 deletion syndrome. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1611527"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1159\/000452815","article-title":"Deletion of TOP3B Is Associated with Cognitive Impairment and Facial Dysmorphism","volume":"150","author":"Kaufman","year":"2016","journal-title":"Cytogenet. Genome Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"D1243","DOI":"10.1093\/nar\/gkae974","article-title":"The UCSC Genome Browser database: 2025 update","volume":"53","author":"Perez","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1101\/gr.5986507","article-title":"Low copy repeats mediate distal chromosome 22q11.2 deletions: Sequence analysis predicts breakpoint mechanisms","volume":"17","author":"Shaikh","year":"2007","journal-title":"Genome Res."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Vervoort, L., Dierckxsens, N., Pereboom, Z., Capozzi, O., Rocchi, M., Shaikh, T.H., and Vermeesch, J.R. (2021). 22q11.2 Low Copy Repeats Expanded in the Human Lineage. Front. Genet., 12.","DOI":"10.3389\/fgene.2021.706641"},{"key":"ref_77","unstructured":"Adam, M.P., Bick, S., Mirzaa, G.M., Pagon, R.A., Wallace, S.E., and Amemiya, A. (1993). 22q11.2 Deletion Syndrome. GeneReviews\u00ae, University of Washington."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1097\/DBP.0000000000000210","article-title":"Behavioral and Psychiatric Phenotypes in 22q11.2 Deletion Syndrome","volume":"36","author":"Tang","year":"2015","journal-title":"J. Dev. Behav. Pediatr."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2015","DOI":"10.1111\/imj.16534","article-title":"Phenotype of patients with late diagnosis of 22q11 deletion: A review and retrospective study","volume":"54","author":"Loh","year":"2024","journal-title":"Intern. Med. J."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Costagliola, G., Legitimo, A., Bertini, V., Alberio, A.M.Q., Valetto, A., and Consolini, R. (2023). Distinct Immunophenotypic Features in Patients Affected by 22q11.2 Deletion Syndrome with Immune Dysregulation and Infectious Phenotype. J. Clin. Med., 12.","DOI":"10.3390\/jcm12247579"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1007\/s00404-025-08041-3","article-title":"Correlation between 22q11.2 deletion syndrome phenotype and deletion location: A meta-analysis","volume":"312","author":"Li","year":"2025","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Bertini, V., Cambi, F., Legitimo, A., Costagliola, G., Consolini, R., and Valetto, A. (2025). 22q11.21 Deletions: A Review on the Interval Mediated by Low-Copy Repeats C and D. Genes, 16.","DOI":"10.3390\/genes16010072"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Delihas, N. (2018). Formation of a Family of Long Intergenic Noncoding RNA Genes with an Embedded Translocation Breakpoint Motif in Human Chromosomal Low Copy Repeats of 22q11.2-Some Surprises and Questions. Non-Coding RNA, 4.","DOI":"10.3390\/ncrna4030016"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"3754","DOI":"10.1093\/hmg\/ddw221","article-title":"Variant discovery and breakpoint region prediction for studying the human 22q11.2 deletion using BAC clone and whole genome sequencing analysis","volume":"25","author":"Guo","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Delihas, N. (2022). An ancestral genomic sequence that serves as a nucleation site for de novo gene birth. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0267864"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1086\/302343","article-title":"Low-copy repeats mediate the common 3-Mb deletion in patients with velo-cardio-facial syndrome","volume":"64","author":"Edelmann","year":"1999","journal-title":"Am. J. Hum. Genet."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1002\/gcc.22952","article-title":"Frequent breakpoints of focal deletion and uniparental disomy in 22q11.1 or 11.2 segmental duplication region reveal distinct tumorigenesis in rhabdoid tumor of the kidney","volume":"60","author":"Haruta","year":"2021","journal-title":"Genes Chromosomes Cancer"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2366","DOI":"10.1002\/ajmg.a.38319","article-title":"The immune deficiency of chromosome 22q11.2 deletion syndrome","volume":"173","author":"Morsheimer","year":"2017","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1016\/j.jpeds.2012.06.018","article-title":"Immunoglobulin deficiencies: The B-lymphocyte side of DiGeorge Syndrome","volume":"161","author":"Patel","year":"2012","journal-title":"J. Pediatr."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/17\/2\/248\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T10:10:29Z","timestamp":1771841429000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/17\/2\/248"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,22]]},"references-count":89,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["genes17020248"],"URL":"https:\/\/doi.org\/10.3390\/genes17020248","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,22]]}}}