{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T14:21:15Z","timestamp":1792333275233,"version":"4.4.0"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,10,8]],"date-time":"2019-10-08T00:00:00Z","timestamp":1570492800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,10,8]],"date-time":"2019-10-08T00:00:00Z","timestamp":1570492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hereditary spastic paraplegia (HSP) comprises a heterogeneous group of neurodegenerative disorders, it share common symptom - of progressive lower spastic paraparesis. The most common autosomal dominant (AD) forms of HSP are SPG4 (<jats:italic>SPAST<\/jats:italic> gene) and SPG3 (<jats:italic>ATL1<\/jats:italic> gene). In the current research we investigated for the first time the distribution of pathogenic mutations in <jats:italic>SPAST<\/jats:italic> and <jats:italic>ATL1<\/jats:italic> genes within a large cohort of Russian HSP patients (122 probands; 69 famillial cases). We determined the frequencies of genetic abnormalities using Sanger sequencing, multiplex ligation-dependent probe amplification (MLPA), and Next Generation Sequencing (NGS) of targeted gene panels. As a result, SPG4 was diagnosed in 30.3% (37\/122) of HSP cases, where the familial cases represented 37.7% (26\/69) of SPG4. In total 31 pathogenic and likely pathogenic variants were detected in <jats:italic>SPAST<\/jats:italic>, with 14 new mutations. Among all detected <jats:italic>SPAST<\/jats:italic> variants, 29% were gross deletions and duplications. The proportion of SPG3 variants in Russian cohort was 8.2% (10\/122) that were all familial cases. All 10 detected <jats:italic>ATL1<\/jats:italic> mutations were missense substitutions, most of which were in the mutational hot spots of 4, 7, 8, 12 exons, with 2 novel mutations. This work will be helpful for the populational genetics of HSP understanding.<\/jats:p>","DOI":"10.1038\/s41598-019-50911-9","type":"journal-article","created":{"date-parts":[[2019,10,8]],"date-time":"2019-10-08T10:25:35Z","timestamp":1570530335000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Mutational Spectrum of Spast (Spg4) and Atl1 (Spg3a) Genes In Russian Patients With Hereditary Spastic Paraplegia"],"prefix":"10.1038","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1245-4881","authenticated-orcid":false,"given":"V. 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