{"id":385,"date":"2024-01-22T00:00:00","date_gmt":"2024-01-22T00:00:00","guid":{"rendered":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2023.1322462"},"modified":"2024-01-22T00:00:00","modified_gmt":"2024-01-22T00:00:00","slug":"the-value-of-genome-wide-analysis-in-craniosynostosis","status":"publish","type":"post","link":"https:\/\/sebigec.es\/blog\/index.php\/2024\/01\/22\/the-value-of-genome-wide-analysis-in-craniosynostosis\/","title":{"rendered":"The value of genome-wide analysis in craniosynostosis"},"content":{"rendered":"<p><bold>Background:<\/bold> This study assessed the diagnostic yield of high-throughput sequencing methods in a cohort of craniosynostosis (CS) patients not presenting causal variants identified through previous targeted analysis.<\/p><p><bold>Methods:<\/bold> Whole-genome or whole-exome sequencing (WGS\/WES) was performed in a cohort of 59 patients (from 57 families) assessed by retrospective phenotyping as having syndromic or nonsyndromic CS.<\/p><p><bold>Results:<\/bold> A syndromic form was identified in 51% of the unrelated cases. A genetic cause was identified in 38% of syndromic cases, with novel variants detected in <italic>FGFR2<\/italic> (a rare Alu insertion), <italic>TWIST1, TCF12, KIAA0586, HDAC9, FOXP1<\/italic>, and <italic>NSD2<\/italic>. Additionally, we report two patients with rare recurrent variants in <italic>KAT6A<\/italic> and <italic>YY1<\/italic> as well as two patients with structural genomic aberrations: one with a 22q13 duplication and one with a complex rearrangement involving chromosome 2 (2p25 duplication including <italic>SOX11<\/italic> and deletion of 2q22). Moreover, we identified potentially relevant variants in 87% of the remaining families with no previously detected causal variants, including novel variants in <italic>ADAMTSL4, ASH1L, ATRX, C2CD3, CHD5, ERF, H4C5, IFT122, IFT140, KDM6B, KMT2D, LTBP1, MAP3K7, NOTCH2, NSD1, SOS1, SPRY1, POLR2A, PRRX1, RECQL4, TAB2, TAOK1, TET3, TGFBR1, TCF20<\/italic>, and <italic>ZBTB20<\/italic>.<\/p><p><bold>Conclusion:<\/bold> These results confirm WGS\/WES as a powerful diagnostic tool capable of either targeted <italic>in silico<\/italic> or broad genomic analysis depending on phenotypic presentation (e.g., classical or unusual forms of syndromic CS).<\/p>","protected":false},"excerpt":{"rendered":"<p>Background: This study assessed the diagnostic yield of high-throughput sequencing methods in a cohort of craniosynostosis (CS) patients not presenting causal variants identified through previous targeted analysis.Methods: Whole-genome or whole-exome s&#8230;<\/p>\n","protected":false},"author":85,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[6,12,13],"tags":[],"class_list":["post-385","post","type-post","status-publish","format-standard","hentry","category-articulos","category-enfermedades-raras","category-frontiers-in-genetics"],"_links":{"self":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts\/385","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/users\/85"}],"replies":[{"embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/comments?post=385"}],"version-history":[{"count":1,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts\/385\/revisions"}],"predecessor-version":[{"id":386,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts\/385\/revisions\/386"}],"wp:attachment":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/media?parent=385"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/categories?post=385"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/tags?post=385"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}