{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T16:09:36Z","timestamp":1791216576973,"version":"4.1.0"},"reference-count":19,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2010,3,26]],"date-time":"2010-03-26T00:00:00Z","timestamp":1269561600000},"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":[[2010,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The concept of the Down syndrome critical region implies the existence of several dosage\u2010sensitive genes that result in an abnormal phenotype when duplicated. Among the genes in the presumed Down syndrome critical region, <jats:italic>DYRK1A<\/jats:italic> and <jats:italic>SIM2<\/jats:italic> are thought to be particularly important because of their critical roles in the development of the central nervous system in model organisms. Considering that regulatory imbalances resulting in an altered amount of expression from crucial target genes tend to produce phenotypic effects in both monosomics and trisomics, haploinsufficiency for the Down syndrome critical region is expected to be associated with an abnormal phenotype. We report on a patient with severe microcephaly, a developmental delay, hypospadias, and corneal opacity who had a microdeletion spanning the Down syndrome critical region, including <jats:italic>DYRK1A<\/jats:italic> and <jats:italic>SIM2<\/jats:italic>. He presented with intrauterine growth retardation, hypospadias, corneal clouding, arched eyebrows, upslanting and narrow palpebral fissures, bifid uvula, prominent nasal root, short columella, prominent central incisors, pegged shaped teeth, retrognathia, hypoplastic nipples, and severe developmental delay. His G\u2010banded karyotype was normal, but array comparative genomic hybridization showed a de novo deletion of 3.97\u2009Mb at chromosome 21q22. The extreme degree of microcephaly in this patient may be ascribed to the haploinsufficiency of <jats:italic>DYRK1A<\/jats:italic>, since brain size is severely reduced in heterozygotes for the <jats:italic>Dyrk1a<\/jats:italic> null mutation in mice. \u00a9 2010 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.a.33228","type":"journal-article","created":{"date-parts":[[2010,3,26]],"date-time":"2010-03-26T18:17:52Z","timestamp":1269627472000},"page":"950-953","source":"Crossref","is-referenced-by-count":31,"title":["Microdeletion of the Down syndrome critical region at 21q22"],"prefix":"10.1002","volume":"152A","author":[{"given":"Hideki","family":"Fujita","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiharu","family":"Torii","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rika","family":"Kosaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinya","family":"Yamaguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Kudoh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kumiko","family":"Hayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takao","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenjiro","family":"Kosaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2010,3,26]]},"reference":[{"key":"e_1_2_4_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.18.1915"},{"key":"e_1_2_4_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2008.89"},{"key":"e_1_2_4_4_1","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.2001.0262"},{"key":"e_1_2_4_5_1","first-page":"62","article-title":"Molecular mapping of 21 features associated with partial monosomy 21: Involvement of the APP\u2010SOD1 region","volume":"57","author":"Chettouh Z","year":"1995","journal-title":"Am J Hum Genet"},{"key":"e_1_2_4_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.12.1853"},{"key":"e_1_2_4_7_1","doi-asserted-by":"publisher","DOI":"10.1100\/tsw.2006.319"},{"key":"e_1_2_4_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.1997.tb02442.x"},{"key":"e_1_2_4_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.1995.tb04074.x"},{"key":"e_1_2_4_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.11.4997"},{"key":"e_1_2_4_11_1","first-page":"997","article-title":"Possible narrowed assignment of the loci of monosomy 21\u2010associated microcephaly and intrauterine growth retardation to a 1.2\u2010Mb segment at 21q22.2","volume":"60","author":"Matsumoto N","year":"1997","journal-title":"Am J Hum Genet"},{"key":"e_1_2_4_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.21.3.218"},{"key":"e_1_2_4_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1095-126"},{"key":"e_1_2_4_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320200121"},{"key":"e_1_2_4_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.10116"},{"key":"e_1_2_4_16_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-01-135970"},{"key":"e_1_2_4_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/13793"},{"key":"e_1_2_4_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320590209"},{"key":"e_1_2_4_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00279408"},{"key":"e_1_2_4_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00327128"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.33228","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.33228","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T14:23:38Z","timestamp":1697639018000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.33228"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,3,26]]},"references-count":19,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2010,4]]}},"alternative-id":["10.1002\/ajmg.a.33228"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.33228","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,3,26]]}}}