{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T20:52:34Z","timestamp":1793307154080,"version":"4.5.0"},"reference-count":45,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2019,8,21]],"date-time":"2019-08-21T00:00:00Z","timestamp":1566345600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003921","name":"Department of Health, Australian Government","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003921","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010661","name":"Horizon 2020 Framework Programme","doi-asserted-by":"publisher","award":["EXTEND PROJECT"],"award-info":[{"award-number":["EXTEND PROJECT"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["Pl17\/00380"],"award-info":[{"award-number":["Pl17\/00380"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["Pl17\/02007"],"award-info":[{"award-number":["Pl17\/02007"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Pathogenic variants in the spastic paraplegia type 7 gene cause a complicated hereditary spastic paraplegia phenotype associated with classical features of mitochondrial diseases, including ataxia, progressive external ophthalmoplegia, and deletions of mitochondrial DNA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To better characterize spastic paraplegia type 7 disease with a clinical, genetic, and functional analysis of a Spanish cohort of spastic paraplegia type 7 patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Genetic analysis was performed in patients suspecting hereditary spastic paraplegia and in 1 patient with parkinsonism and Pisa syndrome, through next\u2010generation sequencing, whole\u2010exome sequencing, targeted Sanger sequencing, and multiplex ligation\u2010dependent probe analysis, and blood mitochondrial DNA levels determined by quantitative polymerase chain reaction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Thirty\u2010five patients were found to carry homozygous or compound heterozygous pathogenic variants in the spastic paraplegia type 7 gene. Mean age at onset was 40\u2009years (range, 12\u201363); 63% of spastic paraplegia type 7 patients were male, and three\u2010quarters of all patients had at least one allele with the c.1529C&gt;T (p.Ala510Val) mutation. Eighty percent of the cohort showed a complicated phenotype, combining ataxia and progressive external ophthalmoplegia (65% and 26%, respectively). Parkinsonism was observed in 21% of cases. Analysis of blood mitochondrial DNA indicated that both patients and carriers of spastic paraplegia type 7 pathogenic variants had markedly lower levels of mitochondrial DNA than control subjects (228 per haploid nuclear DNA vs. 176 vs. 573, respectively; <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Parkinsonism is a frequent finding in spastic paraplegia type 7 patients. Spastic paraplegia type 7 pathogenic variants impair mitochondrial DNA homeostasis irrespective of the number of mutant alleles, type of variant, and patient or carrier status. Thus, spastic paraplegia type 7 supports mitochondrial DNA maintenance, and variants in the gene may cause parkinsonism owing to mitochondrial DNA abnormalities. Moreover, mitochondrial DNA blood analysis could be a useful biomarker to detect at risk families. \u00a9 2019 International Parkinson and Movement Disorder Society<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.27812","type":"journal-article","created":{"date-parts":[[2019,8,21]],"date-time":"2019-08-21T15:59:55Z","timestamp":1566403195000},"page":"1547-1561","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["Parkinsonism and spastic paraplegia type 7: Expanding the spectrum of mitochondrial Parkinsonism"],"prefix":"10.1002","volume":"34","author":[{"given":"Beatriz","family":"De la Casa\u2010Fages","sequence":"first","affiliation":[{"name":"Department of Neurology Hospital General Universitario Gregorio Mara\u00f1on  Madrid Spain"},{"name":"Movement Disorders Unit, National Referral Center for rare diseases with Movement Disorders (CSUR) Hospital General Universitario Gregorio Mara\u00f1on  Madrid 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