{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T15:02:54Z","timestamp":1790694174052,"version":"4.1.0"},"reference-count":45,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2014,8,14]],"date-time":"2014-08-14T00:00:00Z","timestamp":1407974400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2014,11]]},"abstract":"<jats:sec><jats:label\/><jats:p>22q11.2 deletion syndrome is one of the most common microdeletion syndromes. Most patients have a deletion resulting from a recombination of low copy repeat blocks LCR22\u2010A and LCR22\u2010D. Loss of the <jats:italic>TBX1<\/jats:italic> gene is considered the most important cause of the phenotype. A limited number of patients with smaller, overlapping deletions distal to the <jats:italic>TBX<\/jats:italic>1 locus have been described in the literature. In these patients, the <jats:italic>CRKL<\/jats:italic> gene is deleted. Haploinsufficiency of this gene has also been implicated in the pathogenesis of 22q11.2 deletion syndrome. To distinguish these deletions (comprising the LCR22\u2010B to LCR22\u2010D region) from the more distal 22q11.2 deletions (located beyond LCR22\u2010D), we propose the term \u201ccentral 22q11.2 deletions\u201d. In the present study we report on 27 new patients with such a deletion. Together with information on previously published cases, we review the clinical findings of 52 patients. The prevalence of congenital heart anomalies and the frequency of de novo deletions in patients with a central deletion are substantially lower than in patients with a common or distal 22q11.2 deletion. Renal and urinary tract malformations, developmental delays, cognitive impairments and behavioral problems seem to be equally frequent as in patients with a common deletion. None of the patients had a cleft palate. Patients with a deletion that also encompassed the <jats:italic>MAPK1<\/jats:italic> gene, located just distal to LCR22\u2010D, have a different and more severe phenotype, characterized by a higher prevalence of congenital heart anomalies, growth restriction and microcephaly. Our results further elucidate genotype\u2010phenotype correlations in 22q11.2 deletion syndrome spectrum. \u00a9 2014 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.36711","type":"journal-article","created":{"date-parts":[[2014,8,14]],"date-time":"2014-08-14T17:06:40Z","timestamp":1408036000000},"page":"2707-2723","source":"Crossref","is-referenced-by-count":67,"title":["Central 22q11.2 deletions"],"prefix":"10.1002","volume":"164","author":[{"given":"Patrick","family":"Rump","sequence":"first","affiliation":[{"name":"University of Groningen University Medical Centre Groningen Department of Genetics Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"de Leeuw","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Radboud University Medical Centre Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthonie J.","family":"van Essen","sequence":"additional","affiliation":[{"name":"University of Groningen University Medical Centre Groningen Department of Genetics Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corien C.","family":"Verschuuren\u2010Bemelmans","sequence":"additional","affiliation":[{"name":"University of Groningen University Medical Centre Groningen Department of Genetics Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hermine E.","family":"Veenstra\u2010Knol","sequence":"additional","affiliation":[{"name":"University of Groningen University Medical Centre Groningen Department of Genetics Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari\u00eblle E.M.","family":"Swinkels","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics University Medical Centre Utrecht Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilma","family":"Oostdijk","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Leiden University Medical Centre Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Ruivenkamp","sequence":"additional","affiliation":[{"name":"Department of Genetics Leiden University Medical Centre Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Willie","family":"Reardon","sequence":"additional","affiliation":[{"name":"National Centre for Medical Genetics Our Lady's Hospital for Sick Children Crumlin Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonja","family":"de Munnik","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Radboud University Medical Centre Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariken","family":"Ruiter","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Radboud University Medical Centre Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayala","family":"Frumkin","sequence":"additional","affiliation":[{"name":"The Monique and Jacques Roboh Department of Genetic Research Hadassah Hebrew University Medical Centre Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorit","family":"Lev","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics Wolfson Medical Centre Holon Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Evers","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics Heidelberg University Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgit","family":"Sikkema\u2010Raddatz","sequence":"additional","affiliation":[{"name":"University of Groningen University Medical Centre Groningen Department of Genetics Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trijnie","family":"Dijkhuizen","sequence":"additional","affiliation":[{"name":"University of Groningen University Medical Centre Groningen Department of Genetics Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Conny M.","family":"van Ravenswaaij\u2010Arts","sequence":"additional","affiliation":[{"name":"University of Groningen University Medical Centre Groningen Department of Genetics Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,8,14]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.GIM.0000144011.97407.B6"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.10914"},{"key":"e_1_2_7_4_1","first-page":"332","article-title":"International 22q11.2 Deletion Syndrome Consortium. 2011. 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