{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T02:57:17Z","timestamp":1788404237157,"version":"build-2803163510"},"reference-count":17,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2017,8,17]],"date-time":"2017-08-17T00:00:00Z","timestamp":1502928000000},"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":[[2017,10]]},"abstract":"<jats:sec><jats:label\/><jats:p>While X\u2010linked intellectual disability (XLID) syndromes pose a diagnostic challenge for clinicians, an increasing number of recognized disorders and their genetic etiologies are providing answers for patients and their families. The availability of clinical exome sequencing is broadening the ability to identify mutations in genes previously unrecognized as causing XLID. In recent years, the <jats:italic>IQSEC2<\/jats:italic> gene, located at Xp11.22, has emerged as the cause of multiple cases of both nonsyndromic and syndromic XLID. Herein we present a case series of six individuals (five males, one female) with intellectual disability and seizures found to have alterations in <jats:italic>IQSEC2<\/jats:italic>. In all cases, the diagnostic odyssey was extensive and expensive, often including invasive testing such as muscle biopsies, before ultimately reaching the diagnosis. We report these cases to demonstrate the exhaustive work\u2010up prior to finding the changes in <jats:italic>IQSEC2<\/jats:italic> gene, recommend that this gene be considered earlier in the diagnostic evaluation of individuals with global developmental delay, microcephaly, and severe, intractable epilepsy, and support the use of intellectual disability panels including <jats:italic>IQSEC2<\/jats:italic> in the first\u2010line evaluation of these patients.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.38404","type":"journal-article","created":{"date-parts":[[2017,8,17]],"date-time":"2017-08-17T08:14:09Z","timestamp":1502957649000},"page":"2814-2820","source":"Crossref","is-referenced-by-count":18,"title":["The role of <i>IQSEC2<\/i> in syndromic intellectual disability: Narrowing the diagnostic odyssey"],"prefix":"10.1002","volume":"173","author":[{"given":"Benjamin M.","family":"Helm","sequence":"first","affiliation":[{"name":"Department of Medical and Molecular Genetics Indiana University School of Medicine and Riley Hospital for Children at IU Health Indianapolis Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoe","family":"Powis","sequence":"additional","affiliation":[{"name":"Ambry Genetics Department of Clinical Genomics Aliso Viejo California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos E.","family":"Prada","sequence":"additional","affiliation":[{"name":"Division of Human Genetics Department of Pediatrics Cincinnati Children's Hospital Medical Center University of Cincinnati College of Medicine Cincinnati Ohio"},{"name":"Centro de Medicina Genomica y Metabolismo Fundaci\u00f3n Cardiovascular de Colombia Floridablanca Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga L.","family":"Casasbuenas\u2010Alarcon","sequence":"additional","affiliation":[{"name":"Servicio de Neurolog\u00eda Pediatrica Clinica Reina Sof\u00eda Bogota Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tonya","family":"Balmakund","sequence":"additional","affiliation":[{"name":"Division of Neurology Department of Pediatrics University of Arkansas for Medical Sciences Little Rock Arkansas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1236-0017","authenticated-orcid":false,"given":"G. B.","family":"Schaefer","sequence":"additional","affiliation":[{"name":"Section of Genetics and Metabolism Department of Pediatrics University of Arkansas for Medical Sciences Little Rock Arkansas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen G.","family":"Kahler","sequence":"additional","affiliation":[{"name":"Section of Genetics and Metabolism Department of Pediatrics University of Arkansas for Medical Sciences Little Rock Arkansas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Kaylor","sequence":"additional","affiliation":[{"name":"Arkansas Children's Hospital Little Rock Arkansas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Winter","sequence":"additional","affiliation":[{"name":"Valley Children's Hospital Department of Genetic Medicine and Metabolism Madera California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8235-6200","authenticated-orcid":false,"given":"Yuri A.","family":"Zarate","sequence":"additional","affiliation":[{"name":"Section of Genetics and Metabolism Department of Pediatrics University of Arkansas for Medical Sciences Little Rock Arkansas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9194-0644","authenticated-orcid":false,"given":"Samantha A.","family":"Schrier Vergano","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics and Metabolism Children's Hospital of The King's Daughters Norfolk Virginia"},{"name":"Department of Pediatrics Eastern Virginia Medical School Norfolk Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,8,17]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/YPG.0000000000000128"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-011-1011-z"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11080"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature03479"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10897-013-9671-6"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2015.00085"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.02.018"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2015.123"},{"key":"e_1_2_8_10_1","first-page":"33","article-title":"Disruption of the IQSEC2 transcript in a female with X;autosome translocation t(X;20)(p11.2;q11.2) and a phenotype resembling X\u2010linked infantile spasms (ISSX) syndrome","volume":"1","author":"Morleo M.","year":"2008","journal-title":"Molecular Medicine Reports"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80933-2"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.588"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.4161\/sgtp.1.2.13285"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36179"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2013.113"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neures.2016.06.007"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13560"}],"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.38404","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.38404","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.38404","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.38404","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T22:32:10Z","timestamp":1693348330000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.38404"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,8,17]]},"references-count":17,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2017,10]]}},"alternative-id":["10.1002\/ajmg.a.38404"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.38404","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,8,17]]}}}