{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T04:41:53Z","timestamp":1791348113723,"version":"4.3.1"},"reference-count":10,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2015,9,4]],"date-time":"2015-09-04T00:00:00Z","timestamp":1441324800000},"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":[[2015,12]]},"abstract":"<jats:sec><jats:label\/><jats:p>Intellectual disability (ID) is estimated to affect 1\u20133% of the general population and is a common reason for referrals to pediatric and adult geneticists, as well as neurologists. There are many genetic and non\u2010genetic causes of ID; X\u2010linked forms are identifiable through their characteristic inheritance pattern. Current testing methods have been able to identify over 100 genes on the X chromosome responsible for X\u2010linked intellectual disability (XLID) syndromes. <jats:italic>MED12<\/jats:italic> [MIM *300188] (mediator complex subunit 12) mutations have been linked to numerous XLID syndromes, including Lujan, FG, and Ohdo, and <jats:italic>MED12<\/jats:italic> is included in many XLID panels. <jats:italic>MED12<\/jats:italic> is located at Xq13.1 and its product has roles in transcriptional activation and repression. We describe two affected male siblings and their unaffected mother with a novel missense mutation in <jats:italic>MED12<\/jats:italic>, c.4147G&gt;A (p.Ala1383Thr). The siblings share some features of Ohdo syndrome, including feeding difficulties, microcephaly, and speech delay. However, additional attributes such as hypertonia, eosinophilic esophagitis, penile chordee, and particular facial dysmorphisms depart sufficiently from individuals previously described such that they appear to represent a new and expanded phenotype. This case lends credence to the evolving theory that the subtypes of Ohdo, and perhaps other <jats:italic>MED12<\/jats:italic> disorders, reflect a spectrum of characteristics, rather than distinct syndromes. As XLID panel testing and whole exome sequencing (WES) becomes a standard of care for affected males, further <jats:italic>MED12<\/jats:italic> mutations will broaden the phenotype of these intriguing disorders and challenge clinicians to rethink the current diagnostic boundaries. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.37354","type":"journal-article","created":{"date-parts":[[2015,9,4]],"date-time":"2015-09-04T06:44:04Z","timestamp":1441349044000},"page":"3180-3185","source":"Crossref","is-referenced-by-count":20,"title":["Beyond Ohdo syndrome: A familial missense mutation broadens the <i>MED12<\/i> spectrum"],"prefix":"10.1002","volume":"167","author":[{"given":"Katherine G.","family":"Langley","sequence":"first","affiliation":[{"name":"Department of Pediatrics Eastern Virginia Medical School Norfolk Virginia"},{"name":"Division of Medical Genetics and Metabolism Children's Hospital of The King's Daughters Norfolk Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan","family":"Brown","sequence":"additional","affiliation":[{"name":"George Mason University Fairfax Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J.","family":"Gerber","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Eastern Virginia Medical School Norfolk Virginia"},{"name":"Division of Neurodevelopmental Pediatrics Naval Medical Center Portsmouth Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janelle","family":"Fox","sequence":"additional","affiliation":[{"name":"Division of Pediatric Urology Naval Medical Center Portsmouth Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Friez","sequence":"additional","affiliation":[{"name":"Greenwood Genetic Center South Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Lyons","sequence":"additional","affiliation":[{"name":"Greenwood Genetic Center South Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha A.","family":"Schrier Vergano","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Eastern Virginia Medical School Norfolk Virginia"},{"name":"Division of Medical Genetics and Metabolism Children's Hospital of The King's Daughters Norfolk Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,9,4]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1003440"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2011.10.008"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36183"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36539"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36162"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320470618"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.23.3.242"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.35848"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31270"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2013.01.007"}],"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.37354","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.37354","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T23:28:31Z","timestamp":1696634911000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.37354"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,9,4]]},"references-count":10,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2015,12]]}},"alternative-id":["10.1002\/ajmg.a.37354"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.37354","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,9,4]]}}}