{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T10:30:29Z","timestamp":1785148229424,"version":"3.55.0"},"reference-count":43,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,11,10]],"date-time":"2022-11-10T00:00:00Z","timestamp":1668038400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,11,10]],"date-time":"2022-11-10T00:00:00Z","timestamp":1668038400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Nowadays, exome sequencing is a robust and cost-efficient genetic diagnostic tool already implemented in many clinical laboratories. Despite it has undoubtedly improved our diagnostic capacity and has allowed the discovery of many new Mendelian-disease genes, it only provides a molecular diagnosis in up to 25\u201330% of cases. Here, we comprehensively evaluate the results of a large sample set of 4974 clinical exomes performed in our laboratory over a period of 5\u00a0years, showing a global diagnostic rate of 24.62% (1391\/4974). For the evaluation we establish different groups of diseases and demonstrate how the diagnostic rate is not only dependent on the analyzed group of diseases (43.12% in ophthalmological cases vs 16.61% in neurological cases) but on the specific disorder (47.49% in retinal dystrophies vs 24.02% in optic atrophy; 18.88% in neuropathies\/paraparesias vs 11.43% in dementias). We also detail the most frequent mutated genes within each group of disorders and discuss, on our experience, further investigations and directions needed for the benefit of patients.<\/jats:p>","DOI":"10.1038\/s41598-022-23786-6","type":"journal-article","created":{"date-parts":[[2022,11,10]],"date-time":"2022-11-10T15:04:44Z","timestamp":1668092684000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Five years\u2019 experience of the clinical exome sequencing in a Spanish single center"],"prefix":"10.1038","volume":"12","author":[{"given":"A.","family":"Arteche-L\u00f3pez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"\u00c1vila-Fern\u00e1ndez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Riveiro \u00c1lvarez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Almoguera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Bustamante Aragon\u00e9s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I.","family":"Martin-Merida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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Enhanced utility of family-centered diagnostic exome sequencing with inheritance model\u2013based analysis: results from 500 unselected families with undiagnosed genetic conditions. Genet. Med. 17, 578\u2013586 (2014).","journal-title":"Genet. Med."},{"key":"23786_CR9","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.ymgme.2017.04.002","volume":"121","author":"A Alfares","year":"2017","unstructured":"Alfares, A. et al. A multicenter clinical exome study in unselected cohorts from a consanguineous population of Saudi Arabia demonstrated a high diagnostic yield. Mol. Genet. Metab. 121, 91\u201395 (2017).","journal-title":"Mol. Genet. Metab."},{"key":"23786_CR10","doi-asserted-by":"publisher","first-page":"1534","DOI":"10.1177\/0883073816664836","volume":"31","author":"M Kuperberg","year":"2016","unstructured":"Kuperberg, M. et al. Utility of whole exome sequencing for genetic diagnosis of previously undiagnosed pediatric neurology patients. J. Child. 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