{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T02:02:22Z","timestamp":1786413742390,"version":"build-2736575974"},"reference-count":22,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,12,27]],"date-time":"2024-12-27T00:00:00Z","timestamp":1735257600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R01HD093570\u201001A1"],"award-info":[{"award-number":["1R01HD093570\u201001A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Purpose<\/jats:title><jats:p>Heterozygous pathogenic variants in <jats:italic>SPAST<\/jats:italic> are known to cause Hereditary Spastic Paraplegia 4 (SPG4), the most common form of HSP, characterized by progressive bilateral lower limbs spasticity with frequent sphincter disorders. However, there are very few descriptions in the literature of patients carrying biallelic variants in <jats:italic>SPAST<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Targeted Sanger sequencing, panel sequencing and exome sequencing were used to identify the genetic causes in 9 patients from 6 unrelated families with symptoms of HSP or infantile neurodegenerative disorder.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We describe 5 patients with pure HSP with a variable age of onset, mostly in infancy, and 4 patients with profound intellectual disability and progressively worsening tetrapyramidal syndrome. The patients' parents, heterozygous carriers of pathogenic <jats:italic>SPAST<\/jats:italic> variants, included both asymptomatic carriers and patients with classic forms of SPG4.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Biallelic variants of <jats:italic>SPAST<\/jats:italic> may explain cases of hereditary spastic paraplegia with autosomal recessive inheritance. Furthermore, some biallelic variants may also cause psychomotor regression with an infantile neurodegenerative disorder, associated with a tetrapyramidal syndrome, a new phenotype associated with the <jats:italic>SPAST<\/jats:italic> gene.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.70025","type":"journal-article","created":{"date-parts":[[2024,12,28]],"date-time":"2024-12-28T06:59:12Z","timestamp":1735369152000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["From spastic paraplegia to infantile neurodegenerative disorder: Expanding the phenotypic spectrum associated with biallelic <scp><i>SPAST<\/i><\/scp> variants"],"prefix":"10.1111","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-8398-834X","authenticated-orcid":false,"given":"Manon","family":"Degoutin","sequence":"first","affiliation":[{"name":"Service de G\u00e9n\u00e9tique M\u00e9dicale CHU Bordeaux  Bordeaux France"},{"name":"Universit\u00e9 de Bordeaux, UFR Des Sciences m\u00e9dicales  Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5825-5319","authenticated-orcid":false,"given":"Chlo\u00e9","family":"Angelini","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique M\u00e9dicale CHU Bordeaux  Bordeaux France"},{"name":"Centre de r\u00e9f\u00e9rence Maladies Rares \u00ab neurog\u00e9n\u00e9tique \u00bb CHU Bordeaux  Bordeaux France"},{"name":"CNRS, INCIA, UMR 5287, NRGen Team, Univ. 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