{"id":110,"date":"2023-09-21T16:00:19","date_gmt":"2023-09-21T16:00:19","guid":{"rendered":"http:\/\/sebgc.es\/blog\/?guid=d3023002828c9e911c9f8d1867c9900e"},"modified":"2024-01-19T10:35:25","modified_gmt":"2024-01-19T10:35:25","slug":"diagnostic-genome-sequencing-improves-diagnostic-yield-a-prospective-single-centre-study-in-1000-patients-with-inherited-eye-diseases","status":"publish","type":"post","link":"https:\/\/sebigec.es\/blog\/index.php\/2023\/09\/21\/diagnostic-genome-sequencing-improves-diagnostic-yield-a-prospective-single-centre-study-in-1000-patients-with-inherited-eye-diseases\/","title":{"rendered":"Diagnostic genome sequencing improves diagnostic yield: a prospective single-centre study in 1000 patients with inherited eye diseases"},"content":{"rendered":"\n<sec><st>Purpose<\/st>\n<p>Genome sequencing (GS) is expected to reduce the diagnostic gap in rare disease genetics. We aimed to evaluate a scalable framework for genome-based analyses &lsquo;beyond the exome&rsquo; in regular care of patients with inherited retinal degeneration (IRD) or inherited optic neuropathy (ION).<\/p>\n<\/sec>\n<sec><st>Methods<\/st>\n<p>PCR-free short-read GS was performed on 1000 consecutive probands with IRD\/ION in routine diagnostics. Complementary whole-blood RNA-sequencing (RNA-seq) was done in a subset of 74 patients. An open-source bioinformatics analysis pipeline was optimised for structural variant (SV) calling and combined RNA\/DNA variation interpretation.<\/p>\n<\/sec>\n<sec><st>Results<\/st>\n<p>A definite genetic diagnosis was established in 57.4% of cases. For another 16.7%, variants of uncertain significance were identified in known IRD\/ION genes, while the underlying genetic cause remained unresolved in 25.9%. SVs or alterations in non-coding genomic regions made up for 12.7% of the observed variants. The RNA-seq studies supported the classification of two unclear variants.<\/p>\n<\/sec>\n<sec><st>Conclusion<\/st>\n<p>GS is feasible in clinical practice and reliably identifies causal variants in a substantial proportion of individuals. GS extends the diagnostic yield to rare non-coding variants and enables precise determination of SVs. The added diagnostic value of RNA-seq is limited by low expression levels of the major IRD disease genes in blood.<\/p>\n<\/sec>\n","protected":false},"excerpt":{"rendered":"<p>Purpose<br \/>\nGenome sequencing (GS) is expected to reduce the diagnostic gap in rare disease genetics. We aimed to evaluate a scalable framework for genome-based analyses &lsquo;beyond the exome&rsquo; in regular care of patients with inherited retinal deg&#8230;<\/p>\n","protected":false},"author":0,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[6,14,9],"tags":[],"class_list":["post-110","post","type-post","status-publish","format-standard","hentry","category-articulos","category-jmg","category-open-access"],"_links":{"self":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts\/110","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=110"}],"version-history":[{"count":2,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts\/110\/revisions"}],"predecessor-version":[{"id":405,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts\/110\/revisions\/405"}],"wp:attachment":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/media?parent=110"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/categories?post=110"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/tags?post=110"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}