{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T13:47:08Z","timestamp":1762868828649,"version":"3.40.5"},"reference-count":21,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2022,6,9]],"date-time":"2022-06-09T00:00:00Z","timestamp":1654732800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Pediatric B\u2010cell acute lymphoblastic leukemia (B\u2010ALL) is associated with various specific cytogenetic and molecular markers that have significant influence on treatment and prognosis. A subset of children has a much higher risk of developing B\u2010ALL due to constitutional genetic alterations such as trisomy 21 (Down's syndrome). In these patients, B\u2010ALL is often associated with specific genomic profiles leading to leukemic transformation. In rare cases, constitutional structural chromosomal abnormalities involving chromosome 21, such as the der(15;21) Robertsonian translocation and a ring 21 chromosome, have been associated with intrachromosomal amplification of chromosome 21 (iAMP21) B\u2010ALL. Here, we report the development of B\u2010ALL in a child with Down's syndrome who carries a constitutional isodicentric chromosome 21 [idic(21)], described previously by Putra et al., 2017. This idic(21) appeared to be unstable during mitosis, leading to somatic rearrangements consistent with iAMP21 amplification, resulting in the development of leukemia. In this case, a single constitutional structural chromosome 21 rearrangement resulted in a B\u2010ALL with Down syndrome\u2010associated genomic lesions as well as genomic lesions not common to the Down syndrome subtype of B\u2010ALL. Our findings highlight the need for counseling of individuals with constitutional structural chromosome 21 rearrangements regarding their risks of developing a B\u2010ALL.<\/jats:p>","DOI":"10.1002\/ajmg.a.62864","type":"journal-article","created":{"date-parts":[[2022,6,9]],"date-time":"2022-06-09T12:19:39Z","timestamp":1654777179000},"page":"2325-2330","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["B\u2010cell acute lymphoblastic leukemia with <scp>iAMP21<\/scp> in a patient with Down syndrome due to a constitutional isodicentric chromosome 21"],"prefix":"10.1002","volume":"188","author":[{"given":"Angela M.","family":"Verdoni","sequence":"first","affiliation":[{"name":"Department of Obstetrics, Gynecology and Reproductive Sciences University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Megan 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