Retrospective investigation of mutations in the TTR gene in patients diagnosed with transtiethin-related family amyloid polyneuropathy (TTR-FAP)

Objective: Transthyretin-associated familial amyloid polyneuropathy (TTR-FAP) is a rare disease in the general population and is an autosomal dominant, systemic disease caused by the acquisition of toxic function. TTR-FAP develops as a result of the accumulation of amyloid fibrils in various tissues and organs, including peripheral nerve cells, due to mutant TTR protein. The TTR protein is coded by chromosome 18 (18q12.1) and contains 127 amino acids. To date, more than 150 mutations have been identified in the TTR gene. The aim of this study is to investigate the variants in the TTR gene in patients diagnosed with TTR-FAP using DNA sequence analysis. The frequency of the mutations studied will be correlated with the age of onset of the disease, clinical findings, and clinical course. Method: This project is a retrospective study. The genetic test results of patients referred to the Genetic Diseases Diagnostic Center of the Faculty of Medicine at the Mediterranean University with a preliminary diagnosis of TTR-FAP between 2017 and July 2021 and who had DNA sequence analysis for the TTR gene at the Diagnostic Center were scanned and evaluated by comparing the clinical findings of patients with identified mutations. Results: Mutations were identified in 50 out of 423 cases. 21 cases had the c.325 G>C (p.E109Q) variant in exon 3 of the TTR gene. The c.76G>A (p.Gly26Ser) variant in exon 2 of the TTR gene was identified in 25 cases. One of these 25 cases had both the heterozygous c.325 G>C in exon 3 and the c.76G>A genotype in exon 2. In addition, a c.70-9 T>C change in the intronic region 9 nucleotides upstream of exon 2 was detected in 1 case. 3 cases had the c.417G>A (p.Thr139=) variant detected in exon 4 of the TTR gene. Conclusion: It has been determined that the 21 cases with the c.325 G>C variant in exon 3 of the TTR gene are individuals from a single family and 7 families. Key words: TTR-FAP, TTR gene, Retrospective Study