# Novel Pathogenic Variant c.258A>C, p.(Glu86Asp) in the TTR Gene in a Bulgarian Patient with Hereditary Transthyretin Amyloidosis

## TL;DR

A rare genetic mutation in the TTR gene was found in a Bulgarian patient with a hereditary amyloidosis disorder, highlighting the importance of genetic testing for accurate diagnosis.

## Contribution

Identification of a novel pathogenic variant c.258A>C in the TTR gene in a Bulgarian patient with hereditary transthyretin amyloidosis.

## Key findings

- The patient had cardiac dysfunction and was diagnosed with cardiac amyloidosis.
- A heterozygous pathogenic variant c.258A>C, p.(Glu86Asp) in the TTR gene was identified.
- The variant was classified as pathogenic according to ACMG/AMP guidelines.

## Abstract

Hereditary transthyretin amyloidosis (ATTRv) is an autosomal dominant disorder caused by pathogenic variants in the TTR gene. The destabilized mutant form of the transport protein transthyretin (TTR) leads to the extracellular deposition of amyloid fibrils. Materials and Methods: A 65-year-old female patient with suspected clinical diagnosis of ATTR was referred for genetic testing for pathogenic variants in the TTR gene after physical, neurological and cardiac testing. Results: The patient had had cardiac dysfunction, atrial fibrillation and supraventricular tachycardia for around 10 years before the suspected and confirmed cardiac amyloidosis. The molecular genetic testing showed a heterozygous pathogenic variant in exon 3 of the TTR gene NM_000371.4(TTR): c.258A>C, p.(Glu86Asp). This variant in the TTR gene is classified as pathogenic in accordance with ACMG/AMP for the interpretation of variants. Conclusions: The presented case of a very rare pathogenic variant in the TTR gene displays the valuable role of genetic testing on the way to clarifying a diagnosis.