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Alliance"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:p>\n                    We discovered biallelic intragenic structural variations (SVs) in\n                    <jats:italic>FGF12<\/jats:italic>\n                    by applying long-read whole genome sequencing to an exome-negative patient with developmental and epileptic encephalopathy (DEE). We also found another DEE patient carrying a biallelic (homozygous) single-nucleotide variant (SNV) in\n                    <jats:italic>FGF12<\/jats:italic>\n                    that was detected by exome sequencing.\n                    <jats:italic>FGF12<\/jats:italic>\n                    heterozygous recurrent missense variants with gain-of-function or heterozygous entire duplication of\n                    <jats:italic>FGF12<\/jats:italic>\n                    are known causes of epilepsy, but biallelic SNVs\/SVs have never been described.\n                    <jats:italic>FGF12<\/jats:italic>\n                    encodes intracellular proteins interacting with the C-terminal domain of the alpha subunit of voltage-gated sodium channels 1.2, 1.5, and 1.6, promoting excitability by delaying fast inactivation of the channels. To validate the molecular pathomechanisms of these biallelic\n                    <jats:italic>FGF12<\/jats:italic>\n                    SVs\/SNV, highly sensitive gene expression analyses using lymphoblastoid cells from the patient with biallelic SVs, structural considerations, and\n                    <jats:italic>Drosophila<\/jats:italic>\n                    in vivo functional analysis of the SNV were performed, confirming loss-of-function. Our study highlights the importance of small SVs in Mendelian disorders, which may be overlooked by exome sequencing but can be detected efficiently by long-read whole genome sequencing, providing new insights into the pathomechanisms of human diseases.\n                  <\/jats:p>","DOI":"10.26508\/lsa.202302025","type":"journal-article","created":{"date-parts":[[2023,6,7]],"date-time":"2023-06-07T11:30:12Z","timestamp":1686137412000},"page":"e202302025","update-policy":"https:\/\/doi.org\/10.26508\/lsa.crossmarkpolicy","source":"Crossref","is-referenced-by-count":22,"title":["Biallelic structural variations within\n                    <i>FGF12<\/i>\n                    detected by long-read sequencing in 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