{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T07:33:53Z","timestamp":1793432033955,"version":"4.5.0"},"reference-count":25,"publisher":"BMJ","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2009,8,20]]},"published-print":{"date-parts":[[2010,3]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Epilepsy and mental retardation limited to females (EFMR) is an intriguing X-linked disorder affecting heterozygous females and sparing hemizygous males. Mutations in the protocadherin 19 (<jats:italic>PCDH19<\/jats:italic>) gene have been identified in seven unrelated families with EFMR.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>Here, we assessed the frequency of <jats:italic>PCDH19<\/jats:italic> mutations in individuals with clinical features which overlap those of EFMR. We analysed 185 females from three cohorts: 42 with Rett syndrome who were negative for <jats:italic>MECP2<\/jats:italic> and <jats:italic>CDKL5<\/jats:italic> mutations, 57 with autism spectrum disorders, and 86 with epilepsy with or without intellectual disability. No mutations were identified in the Rett syndrome and autism spectrum disorders cohorts suggesting that despite sharing similar clinical characteristics with EFMR, <jats:italic>PCDH19<\/jats:italic> mutations are not generally associated with these disorders. Among the 86 females with epilepsy (of whom 51 had seizure onset before 3\u2005years), with or without intellectual disability, we identified two (2.3%) missense changes. One (c.1671C\u2192G, p.N557K), reported previously without clinical data, was found in two affected sisters, the first EFMR family without a multigenerational family history of affected females. The second, reported here, is a novel de novo missense change identified in a sporadic female. The change, p.S276P, is predicted to result in functional disturbance of PCDH19 as it affects a highly conserved residue adjacent to the adhesion interface of EC3 of PCDH19.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This de novo <jats:italic>PCDH19<\/jats:italic> mutation in a sporadic female highlights that mutational analysis should be considered in isolated instances of girls with infantile onset seizures and developmental delay, in addition to those with the characteristic family history of EFMR.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jmg.2009.068817","type":"journal-article","created":{"date-parts":[[2009,9,14]],"date-time":"2009-09-14T20:45:06Z","timestamp":1252961106000},"page":"211-216","source":"Crossref","is-referenced-by-count":72,"title":["Epilepsy and mental retardation limited to females with <i>PCDH19<\/i> mutations can present de novo or in single generation families"],"prefix":"10.1136","volume":"47","author":[{"given":"Kim","family":"Hynes","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Tarpey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leanne M","family":"Dibbens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta A","family":"Bayly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel F","family":"Berkovic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaella","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zahyia Al","family":"Raisi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha J","family":"Turner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasha J","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tarishi D","family":"Desai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Haan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gillian","family":"Turner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Christodoulou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Leonard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepak","family":"Gill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R","family":"Stratton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jozef","family":"Gecz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid E","family":"Scheffer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2009,9,14]]},"reference":[{"key":"2025101722112413000_47.3.211.1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0997-92"},{"key":"2025101722112413000_47.3.211.2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awm338"},{"key":"2025101722112413000_47.3.211.3","doi-asserted-by":"publisher","DOI":"10.1038\/ng.149"},{"key":"2025101722112413000_47.3.211.4","doi-asserted-by":"crossref","unstructured":"Depienne C Bouteiller D Keren B Cheuret E Poirier K Trouillard O Benyahia B Quelin C Carpentier W Julia S Afenjar A Gautier A Rivier F Meyer S Berquin P H\u00e9lias M Py I Rivera S Bahi-Buisson N Gourfinkel-An I Cazeneuve C Ruberg M Brice A Nabbout R Leguern E . Sporadic infantile epileptic encephalopathy caused by mutations in PCDH19 resembles Dravet syndrome but mainly affects females. PLoS Genet 2009;5:e1000381.","DOI":"10.1371\/journal.pgen.1000381"},{"key":"2025101722112413000_47.3.211.5","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1002\/ajmg.a.10053","article-title":"Effects of MECP2 mutation type, location and X-inactivation in modulating Rett syndrome phenotype","volume":"118","author":"Weaving","year":"2003","journal-title":"Am J Med Genet A"},{"key":"2025101722112413000_47.3.211.6","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M603298200"},{"key":"2025101722112413000_47.3.211.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.12.046"},{"key":"2025101722112413000_47.3.211.8","doi-asserted-by":"crossref","first-page":"2249","DOI":"10.1002\/j.1460-2075.1993.tb05878.x","article-title":"Protocadherins: a large family of cadherin-related molecules in central nervous system","volume":"12","author":"Sano","year":"1993","journal-title":"EMBO J"},{"key":"2025101722112413000_47.3.211.9","doi-asserted-by":"publisher","DOI":"10.1038\/ng.367"},{"key":"2025101722112413000_47.3.211.10","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2004.026237"},{"key":"2025101722112413000_47.3.211.11","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410140412"},{"key":"2025101722112413000_47.3.211.12","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-007-0569-x"},{"key":"2025101722112413000_47.3.211.13","doi-asserted-by":"publisher","DOI":"10.1038\/13810"},{"key":"2025101722112413000_47.3.211.14","doi-asserted-by":"publisher","DOI":"10.1086\/426460"},{"key":"2025101722112413000_47.3.211.15","doi-asserted-by":"publisher","DOI":"10.1086\/426462"},{"key":"2025101722112413000_47.3.211.16","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2007-1641"},{"key":"2025101722112413000_47.3.211.17","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201911"},{"key":"2025101722112413000_47.3.211.18","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2346"},{"key":"2025101722112413000_47.3.211.19","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2007.12.009"},{"key":"2025101722112413000_47.3.211.20","doi-asserted-by":"publisher","DOI":"10.1126\/science.1157657"},{"key":"2025101722112413000_47.3.211.21","unstructured":"Carranza D Dibbens LM Beroric SF Scheffer IE . Do PCDH19 mutations cause Dravet syndrome or a 'pseudo-Dravet' phenotype? Online comment 2009 Apr 12. Sporadic infantile epileptic encephalopathy caused by mutations in PCDH19 resembles Dravet syndrome but mainly affects females. Depienne et al. PLoS Genet 2009."},{"key":"2025101722112413000_47.3.211.22","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M708044200"},{"key":"2025101722112413000_47.3.211.23","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M611725200"},{"key":"2025101722112413000_47.3.211.24","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2009.02.020"},{"key":"2025101722112413000_47.3.211.25","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M705337200"}],"container-title":["Journal of Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jmg.2009.068817","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T05:11:32Z","timestamp":1760764292000},"score":1,"resource":{"primary":{"URL":"https:\/\/jmg.bmj.com\/lookup\/doi\/10.1136\/jmg.2009.068817"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,9,14]]},"references-count":25,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2010,3,19]]},"published-print":{"date-parts":[[2010,3]]}},"alternative-id":["10.1136\/jmg.2009.068817"],"URL":"https:\/\/doi.org\/10.1136\/jmg.2009.068817","relation":{},"ISSN":["0022-2593","1468-6244"],"issn-type":[{"value":"0022-2593","type":"print"},{"value":"1468-6244","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,9,14]]}}}