{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T01:25:26Z","timestamp":1773278726889,"version":"3.50.1"},"reference-count":23,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T00:00:00Z","timestamp":1625097600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T00:00:00Z","timestamp":1625097600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    22q11.2 deletion syndrome (22q11.2 DS, MIM #188400) is the most common chromosomal microdeletion with an incidence of 1 in 4000 live births. 22q11.2 DS patients present with varying penetrance and a broad phenotypic spectrum including dysmorphic features, congenital heart defects, hypoplastic thymus and T\u2010cell deficiency, and hypocalcemia. The typical deletion spans 3\u00a0Mb between 4 large blocks of repetitive DNA, known as low copy repeats (LCRs), on chromosome 22 (LCR22) A\u00a0and D. This deletion is found in ~85% of 22q11.2 DS patients, while only 4\u20135% have central LCR22B\u2010D (1.5\u00a0Mb) and LCR22C\u2010D (0.7\u00a0Mb) deletions. We report on a prenatally diagnosed, inherited case of central LCR22B\u2010D 22q11.2 DS, born to a 22\u2010year\u2010old female with multiple autoimmune disorders. These include Sjogren's\u2010syndrome\u2010related antigen A (SSA+) severe systemic lupus erythematosus (SLE) with cutaneous and discoid components and seronegative antiphospholipid syndrome. Amniocentesis was performed due to fetal growth restriction (FGR). FISH with TUPLE1 (HIRA) probe was normal; however, chromosomal microarray identified a ~737\u2009kb heterozygous loss between LCR22B\u2010D. Subsequently, the same deletion was identified in the mother, which included\n                    <jats:italic>CRKL<\/jats:italic>\n                    and 19 other genes but excluded\n                    <jats:italic>HIRA<\/jats:italic>\n                    and\n                    <jats:italic>TBX1<\/jats:italic>\n                    , the typical candidate genes for 22q11.2DS pathogenesis. This case explores how loss of\n                    <jats:italic>CRKL<\/jats:italic>\n                    may contribute to immune dysregulation, as seen in the multiple severe autoimmune phenotypes of the mother, and FGR. Our experience confirms the importance of thorough workup in individuals with reduced penetrance of 22q11.2 DS features or atypical clinical presentations.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.62346","type":"journal-article","created":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T21:39:40Z","timestamp":1625175580000},"page":"3042-3047","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Central 22q11.2 deletion (\n                    <scp>LCR22 B\u2010D<\/scp>\n                    ) in a fetus with severe fetal growth restriction and a mother with severe systemic lupus erythematosus: Further evidence of\n                    <scp>\n                      <i>CRKL<\/i>\n                    <\/scp>\n                    haploinsufficiency in the pathogenesis of 22q11.2 deletion syndrome"],"prefix":"10.1002","volume":"185","author":[{"given":"Isabella","family":"Lin","sequence":"first","affiliation":[{"name":"David Geffen School of Medicine University of California Los Angeles  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yalda","family":"Afshar","sequence":"additional","affiliation":[{"name":"David Geffen School of Medicine University of California Los Angeles  Los Angeles California USA"},{"name":"Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology University of California Los Angeles  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey","family":"Goldstein","sequence":"additional","affiliation":[{"name":"Pathology and Laboratory Medicine UCLA Center for Health Sciences  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer","family":"Grossman","sequence":"additional","affiliation":[{"name":"David Geffen School of Medicine University of California Los Angeles  Los Angeles California USA"},{"name":"Division of Rheumatology, Department of Medicine University of California Los Angeles  California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wayne W.","family":"Grody","sequence":"additional","affiliation":[{"name":"David Geffen School of Medicine University of California Los Angeles  Los Angeles California USA"},{"name":"Pathology and Laboratory Medicine UCLA Center for Health Sciences  Los Angeles California USA"},{"name":"Department of Human Genetics University of California Los Angeles  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabiola","family":"Quintero\u2010Rivera","sequence":"additional","affiliation":[{"name":"Departments of Pathology and Laboratory Medicine and Pediatrics, Division of Genetic and Genomic Medicine University of California  Irvine California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,7,1]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.40136"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3109\/15513815.2010.487009"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1159\/000438708"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0929-6441(08)60013-2"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2350-15-1"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/apm.12833"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1204779"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2005.12.002"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.200116116"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1067\/mpd.2001.118534"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes11090977"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01730"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11882-018-0823-5"},{"key":"e_1_2_9_15_1","volume-title":"GeneReviews\u00ae [Internet]","author":"McDonald\u2010McGinn D. 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