De la Casa-Fages, BeatrizFernández-Eulate, GorkaGamez, JosepBarahona-Hernando, RaúlMorís, GermánGarcía-Barcina, MaríaInfante, JonZulaica, MirenFernández-Pelayo, UxoaMuñoz-Oreja, MikelUrtasun, MiguelOlaskoaga, AnderZelaya, VictoriaJericó, IvonneSaez-Villaverde, RaquelCatalina, IreneSola Vendrell, EmmaMartínez-Sáez, ElenaPujol, AuroraRuiz, MontserratSchlüter, AgathaSpinazzola, AntonellaMuñoz-Blanco, Jose LuisHolt, IanÁlvarez, VictoriaLópez de Munaín, AdolfoGrandas Pérez, Francisco Javier2024-02-082024-02-082019De la Casa-Fages, B., Fernández-Eulate, G., Gamez, J., Barahona-Hernando, R., Morís, G., García-Barcina, M., Infante, J., Zulaica, M., Fernández-Pelayo, U., Muñoz-Oreja, M., Urtasun, M., Olaskoaga, A., Zelaya, V., Jericó, I., Saez-Villaverde, R., Catalina, I., Sola, E., Martínez-Sáez, E., Pujol, A., Ruiz, M., Schlüter, A., Spinazzola, A., Muñoz-Blanco, J.L., Grandas, F., Holt, I., Álvarez, V. and López de Munaín, A. (2019), Parkinsonism and spastic paraplegia type 7: Expanding the spectrum of mitochondrial Parkinsonism. Mov Disord, 34: 1547-1561. https://doi.org/10.1002/mds.278121547-156110.1002/mds.27812https://hdl.handle.net/20.500.14352/100492Background 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. Objectives 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. Methods Genetic analysis was performed in patients suspecting hereditary spastic paraplegia and in 1 patient with parkinsonism and Pisa syndrome, through next-generation sequencing, whole-exome sequencing, targeted Sanger sequencing, and multiplex ligation-dependent probe analysis, and blood mitochondrial DNA levels determined by quantitative polymerase chain reaction. Results Thirty-five patients were found to carry homozygous or compound heterozygous pathogenic variants in the spastic paraplegia type 7 gene. Mean age at onset was 40 years (range, 12–63); 63% of spastic paraplegia type 7 patients were male, and three-quarters of all patients had at least one allele with the c.1529C>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; P < 0.001). Conclusions 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.engjournal articlehttps://doi.org/10.1002/mds.2781231433872https://pubmed.ncbi.nlm.nih.gov/31433872/restricted access61Hereditary spastic paraplegiaMitochondriaParkinsonismPathogenic genetic variantsSPG7 geneNeurociencias (Medicina)3205.07 Neurología