Hereditary Transthyretin Amyloidosis in Patients Referred to a Genetic Testing Program

Area of Science:

• Genetics
• Cardiovascular Medicine
• Rare Diseases

Background:

• Hereditary amyloid transthyretin (hATTR) amyloidosis diagnosis is often delayed due to overlapping symptoms with other cardiovascular diseases and limited provider awareness.
• The hATTR Compass Genetic Testing Program offered no-cost genetic testing to at-risk individuals.

Purpose of the Study:

• To characterize patients diagnosed with hATTR amyloidosis through genetic testing.
• To raise awareness of genetic testing for hATTR amyloidosis.

Main Methods:

• A cross-sectional, post hoc analysis of patients referred to the hATTR Compass Genetic Testing Program.
• Genetic testing was performed between June 2018 and March 2022.

Main Results:

• A pathogenic TTR variant was identified in 1503 (6.6%) of 22,886 patients.
• The p.V142I TTR variant was the most prevalent (84.0%).
• Black patients represented 23.7% of referred patients and 81.9% of those with the p.V142I variant, with lower reported family history compared to other groups.

Conclusions:

• The genetic testing program successfully identified numerous patients with pathogenic TTR variants.
• The program identified patients in previously unreported geographic regions and historically underrepresented demographic groups.