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. 2025 Feb;71(2):252-256.
doi: 10.1002/mus.28301. Epub 2024 Dec 10.

Prevalence of Pathogenic Transthyretin Gene Variants in the Rocky Mountain Region

Ellie Jacoby  1 , Dianna Quan  1 , Emily Todd  2 , Jonathan Shortt  2 , Harry Smith  2 , Nicholas Rafaels  2 , Kristy Crooks  2   3 ; CCPM biobank Author Banner list
Collaborators, Affiliations

Prevalence of Pathogenic Transthyretin Gene Variants in the Rocky Mountain Region

Ellie Jacoby et al. Muscle Nerve. 2025 Feb.

Abstract

Introduction/aims: Hereditary transthyretin amyloidosis (ATTRv) is a genetic condition caused by pathogenic variants in the transthyretin (TTR) gene resulting in multisystem amyloid deposition, especially in peripheral nerve and heart. Information on the prevalence of ATTRv in the United States is limited. The objective of this study was to understand the prevalence and genetic ancestry in the Val142Ile population in a large regional US population.

Methods: Colorado Center for Personalized Medicine (CCPM) biobank collects specimens from consenting adults seen throughout the University of Colorado Health System, a large tertiary healthcare system within the Rocky Mountain Region (RMR). Single nucleotide polymorphism (SNP) array genotyping and whole exome sequencing (WES) were performed for genetic research. Prevalence of TTR variants was studied.

Results: A total of 73,346 participants had genetic testing; 151 (0.21%) individuals had a pathogenic or likely pathogenic TTR variant. The most common variant was Val142Ile, making up 82.61% of TTR variants found. Over four percent of people with African non-Hispanic ancestry had a Val142Ile variant.

Discussion: The most common TTR variant in our study was Val142Ile, the most common variant in the United States (US). Similar to other US-based studies, affected individuals were predominantly of African, non-Hispanic ancestry. The availability of treatments for symptomatic ATTRv patients raises opportunities and challenges for biobanks as the identification of at-risk individuals places pressure on highly specialized centers and providers to see patients for screening and follow-up.

Keywords: TTR prevalence; Val142Ile; genetics; hereditary amyloidosis; transthyretin.

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