• sequencing
• tdp43

ABSTRACT

Background: Recent advances in immunology techniques lead to identification of TDP-43 protein as a major misfolded disease protein in Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Lobar degeneration (FTLD) with ubiqitinated inclusions. Genetics studies have identified mutations in TARDBP gene (encoding TDP-43) causing disease, suggesting that this protein is directly involved in pathology and not only consequence of disease. Interestingly, mutations in FUS/TLS gene, which share similar functional domains as TARDBP were reported in patients with ALS. These findings could be considered the greatest breakthrough after discover of mutations in SOD1 and progranulin, the major genetic causes in ALS and FTLD-U respectively.
Methods: We have performed genetic analyze by direct sequencing of genes SOD1, PROGRANULIN, TARDBP and FUS (codification regions) in Spanish patients with clinical diagnostic ALS, FTLD and both diseases. Moreover, in 17 from 35 patients TDP-43 pathology was confirmed. Where possible, genomic DNA was extracted from blood (patients) or CNS tissue (autopsies) by standard methods. Results: One mutation in SOD1 was detected and family pedigree of affected individual is showed.