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Many pathogenic <jats:italic>SLC13A5<\/jats:italic> single nucleotide variants (SNVs) and small indels have been described; however, no cases with copy number variants (CNVs) have been sufficiently investigated. We describe a consanguineous Iraqi family harboring an 88.5\u00a0kb homozygous deletion including <jats:italic>SLC13A5<\/jats:italic> in Chr17p13.1. The three affected male siblings exhibit neonatal\u2010onset epilepsy with fever\u2010sensitivity, recurrent status epilepticus, global developmental delay\/intellectual disability (GDD\/ID), and other variable neurological findings as shared phenotypical features of DEE25. Two of the three affected subjects exhibit hypoplastic amelogenesis imperfecta (AI), while the proband shows no evidence of dental abnormalities or AI at 2\u2009years of age with apparently unaffected primary dentition. Characterization of the genomic architecture at this locus revealed evidence for genomic instability generated by an <jats:italic>Alu\/Alu<\/jats:italic>\u2010mediated rearrangement; confirmed by break\u2010point junction Sanger sequencing. This multiplex family from a distinct population elucidates the phenotypic consequence of complete LoF of <jats:italic>SLC13A5<\/jats:italic> and illustrates the importance of read\u2010depth\u2010based CNV detection in comprehensive exome sequencing analysis to solve cases that otherwise remain molecularly unsolved.<\/jats:p>","DOI":"10.1002\/ajmg.a.62192","type":"journal-article","created":{"date-parts":[[2021,4,2]],"date-time":"2021-04-02T07:01:06Z","timestamp":1617346866000},"page":"1972-1980","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["A novel homozygous <scp><i>SLC13A5<\/i><\/scp> whole\u2010gene deletion generated by <scp><i>Alu\/Alu<\/i><\/scp>\u2010mediated rearrangement in an Iraqi family with epileptic encephalopathy"],"prefix":"10.1002","volume":"185","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0401-1877","authenticated-orcid":false,"given":"Ruizhi","family":"Duan","sequence":"first","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7523-6833","authenticated-orcid":false,"given":"Nebal Waill","family":"Saadi","sequence":"additional","affiliation":[{"name":"College of Medicine, University of Baghdad  Baghdad Iraq"},{"name":"Children Welfare Teaching Hospital, Medical City Complex  Baghdad Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3884-7720","authenticated-orcid":false,"given":"Christopher M.","family":"Grochowski","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7361-9221","authenticated-orcid":false,"given":"Ghalia","family":"Bhadila","sequence":"additional","affiliation":[{"name":"Department of Advanced Oral Sciences and Therapeutics University of Maryland School of Dentistry  Baltimore Maryland USA"},{"name":"Department of Pediatric Dentistry, Faculty of Dentistry King AbdulAziz University  Jeddah Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5282-5088","authenticated-orcid":false,"given":"Afnan","family":"Faridoun","sequence":"additional","affiliation":[{"name":"Department of General Dental Practice Faculty of Dentistry, Kuwait University  Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadahiro","family":"Mitani","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9052-1587","authenticated-orcid":false,"given":"Haowei","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3927-2711","authenticated-orcid":false,"given":"Jawid M.","family":"Fatih","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shalini N.","family":"Jhangiani","sequence":"additional","affiliation":[{"name":"Human Genome Sequencing Center, Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9928-9032","authenticated-orcid":false,"given":"Zeynep C.","family":"Akdemir","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1356-5698","authenticated-orcid":false,"given":"Richard A.","family":"Gibbs","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"},{"name":"Human Genome Sequencing Center, Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5788-0270","authenticated-orcid":false,"given":"Davut","family":"Pehlivan","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"},{"name":"Texas Children's Hospital  Houston Texas USA"},{"name":"Section of Pediatric Neurology and Developmental Neuroscience, Department of Pediatrics Baylor College of Medicine &amp; Texas Children's Hospital  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4814-6765","authenticated-orcid":false,"given":"Jennifer E.","family":"Posey","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2233-3423","authenticated-orcid":false,"given":"Dana","family":"Marafi","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"},{"name":"Department of Pediatrics, Faculty of Medicine Kuwait University  Safat Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9907-9246","authenticated-orcid":false,"given":"James R.","family":"Lupski","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"},{"name":"Human Genome Sequencing Center, Baylor College of Medicine  Houston Texas USA"},{"name":"Texas Children's Hospital  Houston Texas USA"},{"name":"Department of Pediatrics Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,4,2]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-015-0173-z"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2014.06.014"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2014.10.006"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-019-0639-5"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/0471142905.hg0723s81"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw1237"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00371.2006"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddv146"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv263"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2020.105018"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2015.09.048"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2018.33"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.2119\/molmed.2016.00077"},{"issue":"2","key":"e_1_2_9_15_1","first-page":"33","article-title":"Opinion tooth hypoplasia for differential diagnosis of childhood epilepsy associated with SLC13A5 mutations","volume":"1","author":"Kopel J. 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