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Sequence analysis of 48 genes was undertaken. Variants were classified using a structured evidence-based approach. Samples were also tested for <jats:italic>C9orf72<\/jats:italic> hexanucleotide expansions using repeat-prime PCR methodology.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>339 pwMND donated a DNA sample: 44 (13.0%) fulfilled criteria for having a pathogenic variant\/repeat expansion, 53.5% of those with a family history of MND and 9.3% of those without. The majority (30 (8.8%)) had a pathogenic <jats:italic>C9orf72<\/jats:italic> repeat expansion, including two with intermediate expansions. Having a <jats:italic>C9orf72<\/jats:italic> expansion was associated with a significantly lower Edinburgh Cognitive and Behavioural ALS Screen ALS-Specific score (<jats:italic>p<\/jats:italic>\u2009=\u20090.0005). The known pathogenic <jats:italic>SOD1<\/jats:italic> variant p.(Ile114Thr), frequently observed in the Scottish population, was detected in 9 (2.7%) of total cases but in 17.9% of familial cases. Rare variants were detected in <jats:italic>FUS<\/jats:italic> and <jats:italic>NEK1<\/jats:italic>. One individual carried both a <jats:italic>C9orf72<\/jats:italic> expansion and <jats:italic>SOD1<\/jats:italic> variant.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Our results provide an accurate summary of MND demographics and genetic epidemiology. We recommend early genetic testing of people with cognitive impairment to ensure that <jats:italic>C9orf72<\/jats:italic> carriers are given the best opportunity for informed treatment planning. Scotland is enriched for the <jats:italic>SOD1<\/jats:italic> p.(Ile114Thr) variant and this has significant implications with regards to future genetically-targeted treatments.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00415-024-12450-w","type":"journal-article","created":{"date-parts":[[2024,6,9]],"date-time":"2024-06-09T08:01:25Z","timestamp":1717920085000},"page":"5256-5266","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Genotypes and phenotypes of motor neuron disease: an update of the genetic landscape in Scotland"],"prefix":"10.1007","volume":"271","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2015-7198","authenticated-orcid":false,"given":"Danielle 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The Scottish MND DNA Bank and the Scottish Regenerative Neurology Tissue Bank are approved by MREC\/98\/0\/56 1989\u20132010, 10\/MRE00\/77 2011 to 2013, 13\/ES\/0126 2013\u20132015, 15\/ES\/0094 2015-present. Ethical permission for the LBC1936 study protocol was obtained from the Multi-Centre Research Ethics Committee for Scotland (Wave 1: MREC\/01\/0\/56), the Lothian Research Ethics Committee (Wave 1: LREC\/2003\/2\/29), and the Scotland A Research Ethics Committee (Waves 2, 3,4 and 5: 07\/MRE00\/58). Ethical permission for the LBC1921 study protocol was obtained from the Lothian Research Ethics Committee (Wave 1: LREC\/1998\/4\/183; Wave 2: LREC\/2003\/7\/23; Wave 3: LREC1702\/98\/4\/183), the Scotland A Research Ethics Committee (Waves 4 and 5: 10\/MRE00\/87).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"All participants provided informed consent to before contributing to the Scottish MND Register\/CARE-MND Platform, Scottish MND DNA Bank and the Scottish Regenerative Neurology Tissue Bank and Lothian Birth Cohorts.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}}]}}