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

Abstract

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

Key words:

• ALS gene sequencing
• C9orf72
• TARDPB
• VAPB
• SOD1

Acknowledgements

We thank Robert Carlone, Brock University, Canada, for critical reading of manuscript and valuable advice.

Declaration of interest

The authors declare that they have no conflict of interests. The authors alone are responsible for the content and writing of this article.

This work was supported by grants from the São Paulo Research Foundation (FAPESP; #2010/20457-7 and #2014/21235-9) and National Council for Scientific and Technological Development (CNPq; 401922/2014-6).

Supplementary material available online