{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T06:36:27Z","timestamp":1788244587210,"version":"build-2803163510"},"reference-count":26,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2013,11,20]],"date-time":"2013-11-20T00:00:00Z","timestamp":1384905600000},"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":[[2014,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Three related males presented with a newly recognized x\u2010linked syndrome associated with neurodegeneration, cutaneous abnormalities, and systemic iron overload. Linkage studies demonstrated that they shared a haplotype on Xp21.3\u2013Xp22.2 and exome sequencing was used to identify candidate variants. Of the segregating variants, only a <jats:italic>PIGA<\/jats:italic> mutation segregated with disease in the family. The c.328_330delCCT <jats:italic>PIGA<\/jats:italic> variant predicts, p.Leu110del (or c.1030_1032delCTT, p.Leu344del depending on the reference sequence). The unaffected great\u2010grandfather shared his X allele with the proband but he did not have the <jats:italic>PIGA<\/jats:italic> mutation, indicating that the mutation arose de novo in his daughter. A single family with a germline <jats:italic>PIGA<\/jats:italic> mutation has been reported; affected males had a phenotype characterized by multiple congenital anomalies and severe neurologic impairment resulting in infantile lethality. In contrast, affected boys in the family described here were born without anomalies and were neurologically normal prior to onset of seizures after 6 months of age, with two surviving to the second decade. <jats:italic>PIGA<\/jats:italic> encodes an enzyme in the GPI anchor biosynthesis pathway. An affected individual in the family studied here was deficient in GPI anchor proteins on granulocytes but not erythrocytes. In conclusion, the PIGA mutation in this family likely causes a reduction in GPI anchor protein cell surface expression in various cell types, resulting in the observed pleiotropic phenotype involving central nervous system, skin, and iron metabolism. \u00a9 2013 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.36189","type":"journal-article","created":{"date-parts":[[2013,11,21]],"date-time":"2013-11-21T00:16:04Z","timestamp":1384992964000},"page":"17-28","source":"Crossref","is-referenced-by-count":67,"title":["A novel germline PIGA mutation in Ferro\u2010Cerebro\u2010Cutaneous syndrome: A neurodegenerative X\u2010linked epileptic encephalopathy with systemic iron\u2010overload"],"prefix":"10.1002","volume":"164","author":[{"given":"Kathryn J.","family":"Swoboda","sequence":"first","affiliation":[{"name":"Pediatric Motor Disorders Research Program Department of Neurology University of Utah School of Medicine Salt Lake City Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca L.","family":"Margraf","sequence":"additional","affiliation":[{"name":"ARUP Institute for Clinical and Experimental Pathology\u00ae, ARUP Laboratories Salt Lake City Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C.","family":"Carey","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology University of Utah School of Medicine Salt Lake City Utah"},{"name":"Department of Pediatrics, Division of Medical Genetics University of Utah School of Medicine Salt Lake City Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holly","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Utah School of Medicine Salt Lake City Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tara M.","family":"Newcomb","sequence":"additional","affiliation":[{"name":"Pediatric Motor Disorders Research Program Department of Neurology University of Utah School of Medicine Salt Lake City Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Coonrod","sequence":"additional","affiliation":[{"name":"ARUP Institute for Clinical and Experimental Pathology\u00ae, ARUP Laboratories Salt Lake City Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Durtschi","sequence":"additional","affiliation":[{"name":"ARUP Institute for Clinical and Experimental Pathology\u00ae, ARUP Laboratories Salt Lake City Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalyan","family":"Mallempati","sequence":"additional","affiliation":[{"name":"ARUP Institute for Clinical and Experimental Pathology\u00ae, ARUP Laboratories Salt Lake City Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Attila","family":"Kumanovics","sequence":"additional","affiliation":[{"name":"ARUP Institute for Clinical and Experimental Pathology\u00ae, ARUP Laboratories Salt Lake City Utah"},{"name":"Department of Pathology University of Utah School of Medicine Salt Lake City Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben E.","family":"Katz","sequence":"additional","affiliation":[{"name":"Private Practice of Pediatrics and Pediatric Neurology Twin Falls Idaho"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl V.","family":"Voelkerding","sequence":"additional","affiliation":[{"name":"ARUP Institute for Clinical and Experimental Pathology\u00ae, ARUP Laboratories Salt Lake City Utah"},{"name":"Department of Pathology University of Utah School of Medicine Salt Lake City Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M.","family":"Opitz","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology University of Utah School of Medicine Salt Lake City Utah"},{"name":"Department of Pediatrics, Division of Medical Genetics University of Utah School of Medicine Salt Lake City Utah"},{"name":"Department of Pathology University of Utah School of Medicine Salt Lake City Utah"},{"name":"Department of Human Genetics University of Utah School of Medicine Salt Lake City Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,11,20]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1410"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa063369"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.2350\/12-02-1155-OA.1"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.806"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.63.1.107"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0022-202X.2004.23227.x"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.34102"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-011-9299-3"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2011.11.031"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.13.7479"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.jbchem.a021746"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/jb\/mvn090"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.653"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2013.03.011"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2009.08.025"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200501038"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)16983-3"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(70)80047-6"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2010.087114"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.02.010"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms13021497"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-08-041004"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.14.7400"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09534"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V83.9.2418.2418"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.3945\/an.110.1009"}],"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.36189","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.36189","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T01:33:30Z","timestamp":1696556010000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.36189"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,11,20]]},"references-count":26,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2014,1]]}},"alternative-id":["10.1002\/ajmg.a.36189"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.36189","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,11,20]]}}}