{"id":13936,"date":"2026-03-31T16:00:34","date_gmt":"2026-03-31T16:00:34","guid":{"rendered":"http:\/\/sebigec.es\/blog\/?guid=40731365483a216fb3ef5bc8c359a4b1"},"modified":"2026-03-31T16:00:34","modified_gmt":"2026-03-31T16:00:34","slug":"the-sines-were-there-identification-of-a-pathogenic-alu-insertion-in-a-patient-with-dicer1-related-tumour-predisposition","status":"publish","type":"post","link":"https:\/\/sebigec.es\/blog\/index.php\/2026\/03\/31\/the-sines-were-there-identification-of-a-pathogenic-alu-insertion-in-a-patient-with-dicer1-related-tumour-predisposition\/","title":{"rendered":"The SINEs were there: identification of a pathogenic Alu insertion in a patient with DICER1-related tumour predisposition"},"content":{"rendered":"<p><I>DICER1<\/I>-related tumour predisposition (DRTP) is an autosomal dominant disorder marked by increased risk of benign and malignant tumours across multiple organ systems. A genetic diagnosis of DRTP requires identification of a (likely) pathogenic germline <I>DICER1<\/I> variant to confirm the diagnosis, and guide clinical management, including cascade testing and surveillance of at-risk relatives.<\/p><p>We report a 14-year-old girl who developed multiple <I>DICER1<\/I>-associated tumours with high clinical suspicion of DRTP. Initial testing via next-generation sequencing and whole genome sequencing revealed only hotspot somatic <I>DICER1<\/I> variants, with no detectable germline variant, complicating the genetic diagnosis.<\/p><p>A structural variant (SV) initially detected in a tumour sample prompted retrospective review of alignment data from all previously tested tumour, blood and normal tissue samples. This revealed a consistent SV across all samples. Short-read data suggested the SV was an Alu element insertion within the RNase IIIa domain of DICER1, but read length was insufficient for conclusive characterisation.<\/p><p>Subsequent long-read nanopore sequencing confirmed a pathogenic AluY insertion, predicted to disrupt DICER1 function.<\/p><p>This case highlights the importance of comprehensive genomic and functional analyses, especially in unresolved cases with strong clinical suspicion. It also demonstrates the value of long-read sequencing in identifying complex variants missed by conventional approaches.<\/p>","protected":false},"excerpt":{"rendered":"<p>DICER1-related tumour predisposition (DRTP) is an autosomal dominant disorder marked by increased risk of benign and malignant tumours across multiple organ systems. A genetic diagnosis of DRTP requires identification of a (likely) pathogenic germline &#8230;<\/p>\n","protected":false},"author":0,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[6,8,9],"tags":[],"class_list":["post-13936","post","type-post","status-publish","format-standard","hentry","category-articulos","category-jmg-first","category-open-access"],"_links":{"self":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts\/13936","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"}],"replies":[{"embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/comments?post=13936"}],"version-history":[{"count":1,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts\/13936\/revisions"}],"predecessor-version":[{"id":13937,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts\/13936\/revisions\/13937"}],"wp:attachment":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/media?parent=13936"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/categories?post=13936"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/tags?post=13936"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}