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We report 19 affected individuals from 10 independent families with ultra\u2010rare bi\u2010allelic <jats:italic>NFU1<\/jats:italic> missense variants associated with a spectrum of early\u2010onset pure to complex hereditary spastic paraplegia (HSP) phenotype with a longer survival (16\/19) on one end and neurodevelopmental delay with severe hypotonia (3\/19) on the other. Reversible or irreversible neurological decompensation after a febrile illness was common in the cohort, and there were invariable white matter abnormalities on neuroimaging. The study suggests that MMDS1 and HSP could be the two ends of the <jats:italic>NFU1<\/jats:italic>\u2010related phenotypic continuum.<\/jats:p>","DOI":"10.1002\/acn3.51679","type":"journal-article","created":{"date-parts":[[2022,10,18]],"date-time":"2022-10-18T15:56:21Z","timestamp":1666108581000},"page":"2025-2035","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Phenotypic continuum of <scp><i>NFU1<\/i><\/scp>\u2010related disorders"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1640-4010","authenticated-orcid":false,"given":"Rauan","family":"Kaiyrzhanov","sequence":"first","affiliation":[{"name":"Department of Neuromuscular Disorders UCL Queen Square Institute of Neurology  London WC1N 3BG UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maha S.","family":"Zaki","sequence":"additional","affiliation":[{"name":"Human Genetics and Genome Research Division, 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