{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T14:23:05Z","timestamp":1747146185009,"version":"3.40.5"},"reference-count":20,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2022,3,23]],"date-time":"2022-03-23T00:00:00Z","timestamp":1647993600000},"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":[[2022,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Haploinsufficiency of <jats:italic>SHOX<\/jats:italic> represents one of the major genetic causes of nonsyndromic short stature. To date, eight DNA elements around <jats:italic>SHOX<\/jats:italic> exons have been proposed as putative enhancer regions. Although six copy\u2010number variations (CNVs) downstream to the known enhancer regions have recently been identified in patients with short stature, the pathogenicity of these CNVs remains uncertain. Here, we identified a paternally derived <jats:italic>SHOX<\/jats:italic> far\u2010downstream deletion in a boy. The deletion involved a ~100\u2009kb genomic interval at a position &gt;60\u2009kb away from the known enhancer regions. The boy exhibited moderate short stature with nonspecific skeletal changes. The height of the father was within the normal range but lower than the mid\u2010parental height. The deletion of the boy and the six previously reported CNVs mostly overlapped; however, all CNVs had unique breakpoints. The deletion of our case encompassed a ~30\u2009kb genomic interval that has previously been associated with a 4C\u2010seq peak, as well as several <jats:italic>SHOX<\/jats:italic>\u2010regulatory SNPs\/indels. These results indicate that the <jats:italic>SHOX<\/jats:italic> far\u2010downstream region contains a novel cis\u2010acting enhancer, whose deletion leads to nonsyndromic short stature of various degree. In addition, our data highlight genomic instability of <jats:italic>SHOX<\/jats:italic>\u2010flanking regions that underlies diverse nonrecurrent CNVs.<\/jats:p>","DOI":"10.1002\/ajmg.a.62734","type":"journal-article","created":{"date-parts":[[2022,3,23]],"date-time":"2022-03-23T12:23:59Z","timestamp":1648038239000},"page":"2173-2177","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<scp><i>SHOX<\/i><\/scp> far\u2010downstream deletion in a patient with nonsyndromic short stature"],"prefix":"10.1002","volume":"188","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9971-4035","authenticated-orcid":false,"given":"Maki","family":"Fukami","sequence":"first","affiliation":[{"name":"Department of Molecular Endocrinology National Research Institute for Child Health and Development  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junya","family":"Shindo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Shizuoka City Shimizu Hospital  Shizuoka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7178-9991","authenticated-orcid":false,"given":"Tsutomu","family":"Ogata","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Hamamatsu University School of Medicine  Hamamatsu Japan"},{"name":"Hamamatsu Medical Center  Hamamatsu Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ikuko","family":"Kageyama","sequence":"additional","affiliation":[{"name":"Department of Molecular Endocrinology National Research Institute for Child Health and Development  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tsutomu","family":"Kamimaki","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Shizuoka City Shimizu Hospital  Shizuoka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,3,23]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2015.165"},{"volume-title":"GeneReviews [Internet]; 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