{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,12]],"date-time":"2026-11-12T17:14:26Z","timestamp":1794503666298,"version":"4.9.1"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,4,28]],"date-time":"2022-04-28T00:00:00Z","timestamp":1651104000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>A variety of hereditary diseases overlap with neurological phenotypes or even share genes with hereditary spastic paraplegia (HSP). The aim of this study was to determine the clinical features and genetic spectrum of patients with clinically suspected HSPs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 52 patients with clinically suspected HSPs were enrolled in this study. All the patients underwent next-generation sequencing (NGS) and triplet repeat primed PCR to screen for the dynamic mutations typical of spinocerebellar ataxia (SCA). Multiplex ligation-dependent probe amplification (MLPA) was further conducted in patients with no causative genetic mutations detected to examine for large deletions and duplications in genes of <jats:italic>SPAST, ATL1, REEP1, PGN, and SPG11<\/jats:italic>. Clinical characteristics and findings of brain MRI were analyzed in patients with definite diagnoses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The mean age of the patients studied was 36.90 \u00b1 14.57 years. 75% (39\/52) of patients manifested a phenotype of complex form of HSPs. A genetic diagnosis was made in 51.9% (27\/52) of patients, of whom 40.3% (21\/52) of patients had mutations in HSPs genes (<jats:italic>SPG4\/SPG6\/SPG8\/SPG11\/SPG15\/SPG78\/SPG5A<\/jats:italic>) and 11.5% (6\/52) of patients had mutations in SCAs genes (<jats:italic>SCA3\/SCA17\/SCA28<\/jats:italic>). SPG4 and SPG11 were the most common cause of pure form of HSPs (5\/6, 83.3%) and complex form of HSPs (5\/15, 33.3%), respectively. Gait disturbance was the most common initial symptom in both the patients with HSPs (15\/21) and in patients with SCAs (5\/6). Dysarthria and cerebellar ataxia were detected in 28.5% (6\/21) and 23.8% (5\/21) of patients with HSPs, respectively, and were the most common symptoms in addition to progressive weakness and spasticity of the lower limbs. Cerebellar atrophy was seen on the brain MRI of patients with SPG5A, SCA3, and SCA28.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Causative genetic mutations were identified in 51.9% of patients with clinically suspected HSPs by NGS and triplet repeat primed PCR. A final diagnosis of HSPs or SCAs was made in 40.3% and 11.5% of patients, respectively. The clinical manifestations and neuroimaging findings overlapped between patients with HSPs and patients with SCAs. Dynamic mutations should be screened in patients with clinically suspected HSPs, especially in those with phenotypes of complex form of HSPs.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneur.2022.872927","type":"journal-article","created":{"date-parts":[[2022,4,28]],"date-time":"2022-04-28T16:05:40Z","timestamp":1651161940000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Clinical Features and Genetic Spectrum of Patients With Clinically Suspected Hereditary Progressive Spastic Paraplegia"],"prefix":"10.3389","volume":"13","author":[{"given":"Yuzhi","family":"Shi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"An","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songtao","family":"Niu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaowu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zaiqiang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,4,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1002\/mdc3.12184","article-title":"An update on the hereditary spastic paraplegias: new genes and new disease models","volume":"2","author":"Kumar","year":"2015","journal-title":"Mov Disord Clin Pract."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jns.2012.03.025","article-title":"Hereditary spastic paraplegias with autosomal dominant, recessive, X-linked, or maternal trait of inheritance","volume":"318","author":"Finsterer","year":"2012","journal-title":"J Neurol Sci."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1697","DOI":"10.3390\/ijms23031697","article-title":"Hereditary spastic paraplegia: an update","volume":"23","author":"Meyyazhagan","year":"2022","journal-title":"Int J Mol Sci."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1601","DOI":"10.1007\/s00415-014-7598-y","article-title":"Diagnosis, investigation and management of hereditary spastic paraplegias in the era of next-generation sequencing","volume":"262","author":"Hensiek","year":"2015","journal-title":"J Neurol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"e513","DOI":"10.1002\/mgg3.513","article-title":"Evaluation of copy number variant detection from panel-based next-generation sequencing data","volume":"7","author":"Yao","year":"2019","journal-title":"Mol Genet Genomic Med."},{"key":"B6","doi-asserted-by":"publisher","first-page":"S1","DOI":"10.1186\/1471-2105-14-S11-S1","article-title":"Computational tools for copy number variation (CNV) detection using next-generation sequencing data: features and perspectives","volume":"14","author":"Zhao","year":"2013","journal-title":"BMC Bioinformatics."},{"key":"B7","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1007\/s11910-021-01099-x","article-title":"Kishore &, Kumar R. 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