C9ORF72, SOD1, tardbp, fus and ubqln2 gene mutations screening in patients who diagnosed with sporadic amyotrophic lateral sclerosis(ALS)

Objective: The aim of this study is to determine existence and frequency of the mutation in C9orf72, SOD1, TARDBP, FUS and UBQLN2 genes which are most frequently observed in sporadic ALS diagnosed cases. Method: Genomic DNA isolation was performed from peripheral blood samples of 10 patients with sporadic ALS. In these patients the C9orf72 gene repeat number was checked by triplet-primer PCR method amplification. All sequences encoding the SOD1, TARDBP, FUS and UBQLN2 genes were screened by DNA sequencing. Results: In 2 of 10 cases c.-45+162_-45+163insGGGGCC change was detected in the first intron of C9orf72 gene as 20 % heterozygous form; in 4 cases c.72+133 C>T change was detected at the first intron of SOD1gene as heterozygous form; in 6 cases c.714+67_714+68insG change was detected in the fifth intron of TARDBP gene as % 60 homozygous form. In the FUS gene mutation screening revealed 2 different genomic changes as c.147C>A change in exon three with 30 % heterozygosity in 3 cases, also in exon four with % 50 heterozygosity in 5 cases and as c.288C>T change with homozygous form in 4 cases. Any genomic change could not have been detected in UBQLN2 gene. Conclusion: An increase in the recurrence rate of C9orf72 hexanucleotide repeat number which is determined as 20 % (2 of 10 cases), suggests that this genomic variation is the most obvious genetic defect in the emergence of sporadic ALS. On the other hand, having one case carrying the increase in C9orf72 hexanucleotide repeat number with carrying genomic changes observed in other cases suggests that these variations are not pathogenic. In addition, a variation in the FUS gene in 9 out of 10 cases strengthens that this gene is highly polymorphic. Key words: ALS, sporadic ALS, gene mutation