{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T12:03:45Z","timestamp":1791115425045,"version":"4.1.0"},"reference-count":25,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2014,3,29]],"date-time":"2014-03-29T00:00:00Z","timestamp":1396051200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT098524MA"],"award-info":[{"award-number":["WT098524MA"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Develop Med Child Neuro"],"published-print":{"date-parts":[[2014,11]]},"abstract":"<jats:p>Homozygous deletions of chromosome 20p12.3, disrupting the promoter region and first three coding exons of the phospholipase C <jats:italic>\u03b2<\/jats:italic>1 gene (<jats:italic><jats:styled-content style=\"fixed-case\">PLCB<\/jats:styled-content>1<\/jats:italic>), have previously been described in two reports of early infantile epileptic encephalopathy (<jats:styled-content style=\"fixed-case\">EIEE<\/jats:styled-content>). Both children were born to consanguineous parents, one presented with infantile spasms, the other with migrating partial seizures of infancy. We describe an infant presenting with severe intractable epilepsy (without a specific <jats:styled-content style=\"fixed-case\">EIEE<\/jats:styled-content> electroclinical syndrome diagnosis) and neurodevelopmental delay associated with compound heterozygous mutations in <jats:italic><jats:styled-content style=\"fixed-case\">PLCB<\/jats:styled-content>1<\/jats:italic>. A case note review and molecular genetic investigations were performed for a child, approximately 10\u00a0months of age, admitted to <jats:styled-content style=\"fixed-case\">J<\/jats:styled-content>ohns <jats:styled-content style=\"fixed-case\">H<\/jats:styled-content>opkins <jats:styled-content style=\"fixed-case\">U<\/jats:styled-content>niversity <jats:styled-content style=\"fixed-case\">H<\/jats:styled-content>ospital for developmental delay and new\u2010onset seizures. The patient presented at 6\u00a0months of age with developmental delay, followed by the onset of intractable, focal, and generalized seizures associated with developmental regression from 10\u00a0months of age. Presently, at 2\u00a0years of age, the child has severe motor and cognitive delays. Diagnostic microarray revealed a heterozygous 476kb deletion of 20p12.3 (encompassing <jats:italic><jats:styled-content style=\"fixed-case\">PLCB<\/jats:styled-content>1<\/jats:italic>), which was also detected in the mother. The genomic breakpoints for the heterozygous deletion were determined. In order to investigate the presence of a second <jats:italic><jats:styled-content style=\"fixed-case\">PLCB<\/jats:styled-content>1<\/jats:italic> mutation, direct Sanger sequencing of the coding region and flanking intronic regions was undertaken, revealing a novel heterozygous intron 1 splice site variant (c.99+1G&gt;A) in both the index individual and the father. Advances in molecular genetic testing have greatly improved diagnostic rates in <jats:styled-content style=\"fixed-case\">EIEE<\/jats:styled-content>, and this report further confirms the important role of microarray investigation in this group of disorders. <jats:italic><jats:styled-content style=\"fixed-case\">PLCB<\/jats:styled-content>1\u2010<\/jats:italic><jats:styled-content style=\"fixed-case\">EIEE<\/jats:styled-content> is now reported in a number of different <jats:styled-content style=\"fixed-case\">EIEE<\/jats:styled-content> phenotypes and our report provides further evidence for phenotypic pleiotropy encountered in early infantile epilepsy syndromes.<\/jats:p>","DOI":"10.1111\/dmcn.12450","type":"journal-article","created":{"date-parts":[[2014,3,29]],"date-time":"2014-03-29T05:12:45Z","timestamp":1396069965000},"page":"1124-1128","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Severe infantile epileptic encephalopathy due to mutations in <i><scp>PLCB<\/scp>1<\/i>: expansion of the genotypic and phenotypic disease spectrum"],"prefix":"10.1111","volume":"56","author":[{"given":"Adeline","family":"Ngoh","sequence":"first","affiliation":[{"name":"Neurosciences Unit Developmental Neurosciences University College London Institute of Child Health London UK"},{"name":"Department of Neurology Great Ormond Street Hospital London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"McTague","sequence":"additional","affiliation":[{"name":"Neurosciences Unit Developmental Neurosciences University College London Institute of Child Health London UK"},{"name":"Department of Neurology Great Ormond Street Hospital London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid M","family":"Wentzensen","sequence":"additional","affiliation":[{"name":"McKusick\u2010Nathans Institute of Genetic Medicine Johns Hopkins University School of Medicine Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Meyer","sequence":"additional","affiliation":[{"name":"Neurosciences Unit Developmental Neurosciences University College London Institute of Child Health London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn","family":"Applegate","sequence":"additional","affiliation":[{"name":"McKusick\u2010Nathans Institute of Genetic Medicine Johns Hopkins University School of Medicine Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric H","family":"Kossoff","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Johns Hopkins University School of Medicine Baltimore MD USA"},{"name":"Department of Neurology Johns Hopkins University School of Medicine Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise 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