Genetic analysis of patients with familial and sporadic amyotrophic lateral sclerosis in a Brazilian Research Center

<i>Objective</i>: To investigate gene mutations in familial form (FALS) and sporadic form (SALS) of amyotrophic lateral sclerosis (ALS) in a highly miscegenated population. <i>Methods</i>: Frequencies of mutations in the <i>C9orfF72</i>, <i>TARDBP</i>, <i>SOD1</i>, <i>FUS</i> and <i>VAPB</i> genes were investigated in a cohort of FALS (<i>n</i> = 39) and SALS (<i>n</i> = 189) subjects from the Research Centre of the University of São Paulo School of Medicine. All patients were subjected to <i>C9orf72</i> and <i>TARDBP</i> analyses. <i>SOD1</i>, <i>FUS</i> and <i>VAPB</i> were also evaluated in FALS subjects. <i>Results</i>: Mutations were identified in FALS (61.3%) and SALS (5.3%) patients. Mutations in <i>C9orf72</i> (12.8%, &gt;45 GGGGCC hexanucleotide repeats), <i>VAPB</i> (43.6%, P56S) and <i>SOD1</i> (7.7%, <i>L145S</i>) were identified in FALS subjects. Pathogenic <i>C9orf72</i> expansions (2.64%) were identified in some SALS patients. Similar changes of <i>TARDBP</i> were found in SALS (2.64%) but not in FALS subjects. No <i>FUS</i> mutations were seen in any FALS subjects. <i>Conclusions</i>: <i>TARDBP</i> and <i>C9orf72</i> mutations in this cohort were similar to those found in other centres worldwide. <i>VAPB</i> mutation (P56S) was highly prevalent in Brazilian FALS patients.