Genetic alterations of C9orf72, SOD1, TARDBP, FUS, and UBQLN2 genes in patients with Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis is the most common motor neuron disease of the adulthood. Genetic analyses performed on cases with sporadic ALS (sALS) and familial ALS (fALS) have revealed mutations most commonly in the genes <i>C9orf72</i>, <i>SOD1</i>, <i>TARDBP</i>, <i>FUS</i>, and <i>UBQLN2</i>. The aim of this study was to investigate the presence and incidence of these most common genomic alterations in these genes of 30 ALS cases. Increase in the number of hexanucleotide repeats within the gene <i>C9orf72</i> was investigated using the fragment analysis method. A heterozygote c.-45 + 162_-45 + 163insGGGGCC alteration was observed in the first intron of the <i>C9orf72</i> gene in only two sALS cases (6.6%), c.72 + 133C&gt;T alteration was observed in the first intron of the SOD1 gene in six fALS and two sALS cases (26.6%), a c.169 + 41C&gt;A alteration was observed in the second intron of the same gene in one case, a c.239 + 34A&gt;C alteration was observed in the third intron of the same gene in three fALS cases (10%), and a c.714 + 67_714 + 68insG alteration was observed in the fifth intron of the TARDBP gene in six sALS cases (20%). Three different genomic alterations were detected in the <i>FUS</i> gene; two silent variants p.G49G (c.147C&gt;A) in 3 cases (10%) and p.Y97Y (c.291C&gt;T) in 25 cases (83%) and an intronic variant c.1067-61T˃C in 4 cases (13%). A novel missense variant, p.G457H (c.1371G&gt;C), was observed in the <i>UBQLN2</i> gene in one case with sALS. Our study has revealed three novel and previously reported genomic alterations in the ALS-related genes.