{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T07:10:03Z","timestamp":1756278603978,"version":"3.44.0"},"reference-count":20,"publisher":"BMJ","issue":"4","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Case Rep"],"accepted":{"date-parts":[[2024,4,6]]},"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:p>A man in his 30s was referred to neurology with right-sided paraesthesia, tremors, chest pain and lower urinary tract and erectile dysfunction. He had a medical history of left acetabular dysplasia, and subjective memory impairment, the latter being in the context of depression and chronic pain with opioid use. There was no notable family history. On examination, he had a spastic paraparesis. Imaging revealed atrophy of the thoracic spine. Lumbar puncture demonstrated a raised protein but other constituents were normal, including no presence of oligoclonal bands. Genetic testing revealed a novel heterozygous likely pathogenic SPAST variant c. 1643A&gt;T p.(Asp548Val), confirming the diagnosis of hereditary spastic paraparesis. Symptomatic treatment with physiotherapy and antispasmodic therapy was initiated. This is the first study reporting a patient with this SPAST variant. Ensembl variant effect predictor was used, with the application of computational variant prediction tools providing support that the variant we have identified is likely deleterious and damaging. Our variant CADD score was high, indicating that our identified variant was a highly deleterious substitution.<\/jats:p>","DOI":"10.1136\/bcr-2022-252396","type":"journal-article","created":{"date-parts":[[2024,4,17]],"date-time":"2024-04-17T12:40:37Z","timestamp":1713357637000},"page":"e252396","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Novel genetic variant in hereditary spastic paraparesis"],"prefix":"10.1136","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-7489-5229","authenticated-orcid":false,"given":"Kathryn A W","family":"Knight","sequence":"first","affiliation":[{"name":"Medical School, University of Dundee, Dundee, UK"},{"name":"Department of Neurology, NHS Tayside, Dundee, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4869-768X","authenticated-orcid":false,"given":"Catriona","family":"Barbour-Hastie","sequence":"additional","affiliation":[{"name":"The University of Edinburgh, Edinburgh, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angus","family":"Gane","sequence":"additional","affiliation":[{"name":"The University of Edinburgh, Edinburgh, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan","family":"O'Riordan","sequence":"additional","affiliation":[{"name":"Department of Neurology, NHS Tayside, Dundee, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2024,4,17]]},"reference":[{"key":"2025082623381211000_17.4.e252396.1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-013-1115-8"},{"key":"2025082623381211000_17.4.e252396.2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-59565-2.00060-5"},{"key":"2025082623381211000_17.4.e252396.3","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(08)70258-8"},{"key":"2025082623381211000_17.4.e252396.4","doi-asserted-by":"publisher","DOI":"10.1007\/s10072-020-04981-7"},{"key":"2025082623381211000_17.4.e252396.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2019.03.001"},{"key":"2025082623381211000_17.4.e252396.6","doi-asserted-by":"crossref","first-page":"3331","DOI":"10.1093\/brain\/awy285","article-title":"Spastic Paraplegia due to SPAST mutations is modified by the underlying Mutation and sex","volume":"141","author":"Parodi","year":"2018","journal-title":"Brain"},{"key":"2025082623381211000_17.4.e252396.7","doi-asserted-by":"publisher","DOI":"10.1038\/15472"},{"key":"2025082623381211000_17.4.e252396.8","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1002\/jcp.22341","article-title":"Distinct intracellular Vesicle transport mechanisms are selectively modified by Spastin and Spastin mutations","volume":"226","author":"Fuerst","year":"2011","journal-title":"J Cell Physiol"},{"key":"2025082623381211000_17.4.e252396.9","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2009.201103"},{"key":"2025082623381211000_17.4.e252396.10","doi-asserted-by":"crossref","DOI":"10.1186\/s13059-016-0974-4","article-title":"The Ensembl variant effect Predictor","volume":"17","author":"McLaren","year":"2016","journal-title":"Genome Biol"},{"key":"2025082623381211000_17.4.e252396.11","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks539"},{"key":"2025082623381211000_17.4.e252396.12","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth0410-248"},{"key":"2025082623381211000_17.4.e252396.13","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1016"},{"key":"2025082623381211000_17.4.e252396.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2011.03.043"},{"key":"2025082623381211000_17.4.e252396.15","doi-asserted-by":"publisher","DOI":"10.1002\/ana.10757"},{"key":"2025082623381211000_17.4.e252396.16","doi-asserted-by":"publisher","DOI":"10.1007\/s00234-005-1415-3"},{"key":"2025082623381211000_17.4.e252396.17","doi-asserted-by":"publisher","DOI":"10.1159\/000090294"},{"key":"2025082623381211000_17.4.e252396.18","unstructured":"Parodi L . 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