{Reference Type}: Journal Article
{Title}: Parkinsonism and spastic paraplegia type 7: Expanding the spectrum of mitochondrial Parkinsonism.
{Author}: De 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 JL;Grandas F;Holt I;Álvarez V;López de Munaín A;
{Journal}: Mov Disord
{Volume}: 34
{Issue}: 10
{Year}: 10 2019
{Factor}: 9.698
{DOI}: 10.1002/mds.27812
{Abstract}: 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.<BR>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.<BR>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.<BR>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).<BR>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. © 2019 International Parkinson and Movement Disorder Society.