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CNVs in the 22q11.2 region are mediated by nonallelic homologous recombination between pairs of low copy repeats (LCRs), from amongst eight LCRs designated A\u2010H. Heterozygous distal type II deletions (LCR\u2010E to LCR\u2010F) have incomplete penetrance and variable expressivity, and can lead to neurodevelopmental issues, minor craniofacial anomalies, and congenital abnormalities. We report siblings with global developmental delay, hypotonia, minor craniofacial anomalies, ocular abnormalities, and minor skeletal issues, in whom chromosomal microarray identified a homozygous distal type II deletion. The deletion was brought to homozygosity as a result of a consanguineous marriage between two heterozygous carriers of the deletion. The phenotype of the children was strikingly more severe and complex than that of the parents. This report suggests that the distal type II deletion harbors a dosage\u2010sensitive gene or regulatory element, which leads to a more severe phenotype when deleted on both chromosomes.<\/jats:p>","DOI":"10.1002\/ajmg.a.63326","type":"journal-article","created":{"date-parts":[[2023,6,27]],"date-time":"2023-06-27T07:58:36Z","timestamp":1687852716000},"page":"2623-2630","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Homozygous 22q11.2 distal type <scp>II<\/scp> microdeletion is associated with syndromic neurodevelopmental delay"],"prefix":"10.1002","volume":"191","author":[{"given":"Somaya","family":"Salah","sequence":"first","affiliation":[{"name":"Department of Genetics Hadassah Medical Center  Jerusalem Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiba","family":"Jaber","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Unit Hadassah Medical Center  Jerusalem Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayala","family":"Frumkin","sequence":"additional","affiliation":[{"name":"Department of Genetics Hadassah Medical Center  Jerusalem Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3595-7075","authenticated-orcid":false,"given":"Tamar","family":"Harel","sequence":"additional","affiliation":[{"name":"Department of Genetics Hadassah Medical Center  Jerusalem Israel"},{"name":"Faculty of Medicine Hebrew University of Jerusalem  Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,6,27]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.1083"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1159\/000328135"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/nargab\/lqab037"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/4.4.763"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1159\/000438708"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2015.11.017"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2010.08.002"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw1237"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.39.10.e62"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-005-0104-y"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes13112083"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61969"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2016.132"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/aur.2332"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2013.07.022"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1242\/bio.20148771"},{"issue":"6","key":"e_1_2_9_18_1","first-page":"1377","article-title":"Deletion mapping of 22q11 in CATCH22 syndrome: Identification of a second critical region","volume":"58","author":"Kurahashi H.","year":"1996","journal-title":"American Journal of Human Genetics"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2015.12.008"},{"issue":"6","key":"e_1_2_9_20_1","first-page":"2343","article-title":"The BCR gene and Philadelphia chromosome\u2010positive leukemogenesis","volume":"61","author":"Laurent E.","year":"2001","journal-title":"Cancer Research"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature19057"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2014.01.017"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2012-101320"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2013.79"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2010.04.006"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37351"},{"key":"e_1_2_9_27_1","doi-asserted-by":"crossref","unstructured":"Nik\u2010Zainal S. 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