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Outside the research setting, testing is often restricted to those who report a family history. The aim of this study was to explore the added benefit of offering routine genetic testing to all patients in a regional ALS centre.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p><jats:italic>C9ORF72<\/jats:italic> expansion testing and exome sequencing was offered to consecutive patients (150 with ALS and 12 with primary lateral sclerosis [PLS]) attending the Oxford Motor Neuron Disease Clinic within a defined time period.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 17 (11.3%) highly penetrant pathogenic variants in <jats:italic>C9ORF72<\/jats:italic>, <jats:italic>SOD1<\/jats:italic>, <jats:italic>TARDBP<\/jats:italic>, <jats:italic>FUS<\/jats:italic> and <jats:italic>TBK1<\/jats:italic> were detected, of which 10 were also found through standard clinical genetic testing pathways. The systematic approach resulted in five additional diagnoses of a <jats:italic>C9ORF72<\/jats:italic> expansion (number needed to test [NNT]\u2009=\u200928), and two further missense variants in <jats:italic>TARDBP<\/jats:italic> and <jats:italic>SOD1<\/jats:italic> (NNT\u2009=\u200969). Additionally, 3 patients were found to carry pathogenic risk variants in <jats:italic>NEK1<\/jats:italic>, and 13 patients harboured common missense variants in <jats:italic>CFAP410<\/jats:italic> and <jats:italic>KIF5A<\/jats:italic>, also associated with an increased risk of ALS. We report two novel non\u2010coding loss\u2010of\u2010function splice variants in <jats:italic>TBK1<\/jats:italic> and <jats:italic>OPTN<\/jats:italic>. No relevant variants were found in the PLS patients. Patients were offered double\u2010blinded participation, but &gt;80% requested disclosure of the results.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study provides evidence that expanding genetic testing to all patients with a clinical diagnosis of ALS enhances the potential for recruitment to clinical trials, but will have direct resource implications for genetic counselling.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.15855","type":"journal-article","created":{"date-parts":[[2023,5,10]],"date-time":"2023-05-10T21:26:02Z","timestamp":1683753962000},"page":"2240-2249","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Advantages of routine next\u2010generation sequencing over standard genetic testing in the amyotrophic lateral sclerosis 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