{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T05:13:20Z","timestamp":1791350000320,"version":"4.3.1"},"reference-count":22,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2013,12,4]],"date-time":"2013-12-04T00:00:00Z","timestamp":1386115200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Genetic Counseling"],"published-print":{"date-parts":[[2014,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Intellectual disability is a heterogeneous disorder with a wide phenotypic spectrum. Over 1,700 OMIM genes have been associated with this condition, many of which reside on the X\u2010chromosome. The <jats:italic>IQSEC2<\/jats:italic> gene is located on chromosome Xp11.22 and is known to play a significant role in the maintenance and homeostasis of the brain. Mutations in <jats:italic>IQSEC2<\/jats:italic> have been historically associated with nonsyndromic X\u2010linked intellectual disability. Case reports of affected probands show phenotypic overlap with conditions associated with pathogenic <jats:italic>MECP2<\/jats:italic>, <jats:italic>FOXG1<\/jats:italic>, <jats:italic>CDKL5<\/jats:italic>, and <jats:italic>MEF2C<\/jats:italic> gene mutations. Affected individuals, however, have also been identified as presenting with additional clinical features including seizures, autistic\u2010behavior, psychiatric problems, and delayed language skills. To our knowledge, only 5 deleterious mutations and 2 intragenic duplications have been previously reported in <jats:italic>IQSEC2<\/jats:italic>. Here we report two novel <jats:italic>IQSEC2<\/jats:italic> de novo truncating mutations identified through diagnostic exome sequencing in two severely affected unrelated male probands manifesting developmental delay, seizures, hypotonia, plagiocephaly, and abnormal MRI findings. Overall, diagnostic exome sequencing established a molecular diagnosis for two patients in whom traditional testing methods were uninformative while expanding on the mutational and phenotypic spectrum. In addition, our data suggests that <jats:italic>IQSEC2<\/jats:italic> may be more common than previously appreciated, accounting for approximately 9 % (2\/22) of positive findings among patients with seizures referred for diagnostic exome sequencing. Further, these data supports recently published data suggesting that <jats:italic>IQSEC2<\/jats:italic> plays a more significant role in the development of X\u2010linked intellectual disability with seizures than previously anticipated.<\/jats:p>","DOI":"10.1007\/s10897-013-9671-6","type":"journal-article","created":{"date-parts":[[2013,12,3]],"date-time":"2013-12-03T01:09:03Z","timestamp":1386032943000},"page":"289-298","source":"Crossref","is-referenced-by-count":47,"title":["Diagnostic Exome Sequencing Identifies Two Novel <i>IQSEC2<\/i> Mutations Associated with X\u2010Linked Intellectual Disability with Seizures: Implications for Genetic Counseling and Clinical Diagnosis"],"prefix":"10.1002","volume":"23","author":[{"given":"Stephanie K.","family":"Gandomi","sequence":"first","affiliation":[{"name":"Department of Clinical Genomics Ambry Genetics 15 Argonaut Aliso Viejo CA 92656 USA"},{"name":"2277 Good Pasture Road Placerville CA 95667 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. D.","family":"Farwell Gonzalez","sequence":"additional","affiliation":[{"name":"Department of Clinical Genomics Ambry Genetics 15 Argonaut Aliso Viejo CA 92656 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Parra","sequence":"additional","affiliation":[{"name":"Department of Clinical Genomics Ambry Genetics 15 Argonaut Aliso Viejo CA 92656 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Shahmirzadi","sequence":"additional","affiliation":[{"name":"Department of Clinical Genomics Ambry Genetics 15 Argonaut Aliso Viejo CA 92656 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Mancuso","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Mayo Clinic Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Pichurin","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Mayo Clinic Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Temme","sequence":"additional","affiliation":[{"name":"Department of Genetics Children's Hospital &amp; Clinics of Minnesota St. Paul MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Dugan","sequence":"additional","affiliation":[{"name":"Department of Genetics Children's Hospital &amp; Clinics of Minnesota St. Paul MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W.","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Clinical Genomics Ambry Genetics 15 Argonaut Aliso Viejo CA 92656 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sha","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Clinical Genomics Ambry Genetics 15 Argonaut Aliso Viejo CA 92656 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,12,4]]},"reference":[{"key":"e_1_2_6_2_1","volume-title":"Text Revision (DSM\u2010IV\u2010TR)","author":"American Psychiatric Association","year":"2000"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201595"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/0883073812450209"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2013-14-3-303"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1523"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddh222"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0807765105"},{"key":"e_1_2_6_9_1","first-page":"33","article-title":"Disruption of the IQSEC2 transcript in a female with X;autosome translocation t(X;20)(p 11.2q11.2) 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_6_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/dnares\/5.1.31"},{"key":"e_1_2_6_11_1","unstructured":"Protection of Human Subjects 45 CFR 46.102(d) (2009).Department of Health and Human Servicesretrieved fromhttp:\/\/www.hhs.gov\/ohrp\/humansubjects\/guidance\/45cfr46.html#subparta"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/bmb\/ldr029"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)61480-9"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e31816b5cae"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1754"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12687-012-0092-2"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/29.1.308"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.588"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/gm13"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0012162200000165"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320300151"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature02168"},{"key":"e_1_2_6_23_1","doi-asserted-by":"crossref","unstructured":"Tran Mau\u2010Them F. Willems M. Albrecht B. Sanchez E. Puechberty J. Endele S. et al. (2013).Expanding the phenotype of IQSEC2 mutations: truncating mutations in severe intellectual disability.European Journal of Human Genetics.","DOI":"10.1038\/ejhg.2013.113"}],"container-title":["Journal of Genetic Counseling"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1007\/s10897-013-9671-6","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T01:40:38Z","timestamp":1694742038000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1007\/s10897-013-9671-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,12,4]]},"references-count":22,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2014,6]]}},"alternative-id":["10.1007\/s10897-013-9671-6"],"URL":"https:\/\/doi.org\/10.1007\/s10897-013-9671-6","archive":["Portico"],"relation":{},"ISSN":["1059-7700","1573-3599"],"issn-type":[{"value":"1059-7700","type":"print"},{"value":"1573-3599","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,12,4]]}}}