Presence of the V122I Variant of Hereditary Transthyretin-Mediated Amyloidosis Among Self-Reported White Individuals in a Sponsored Genetic Testing Program

Trachtenberg, Barry; Shah, Sachin; Nussbaum, Robert L.; Bristow, Sara L.; Malladi, Ruthvik; Vatta, Matteo

doi:10.1161/circgen.121.003466

Cited by 8 publications

(1 citation statement)

References 5 publications

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“… 27 In another study with a mixed population of self-reported White and Black individuals with Val122Ile, 20% to 27% reported neuropathy. 36 Early-onset Val30Met predominantly causes polyneuropathy, but late onset often has cardiac involvement. 6 Glu89Gln has a mixed phenotype of polyneuropathy and cardiomyopathy.…”

Section: Geneticsmentioning

confidence: 99%

ATTR Epidemiology, Genetics, and Prognostic Factors

Chukwuemeka

Mostertz

Griffin

et al. 2022

Methodist DeBakey Cardiovascular Journal

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Transthyretin amyloid cardiomyopathy (ATTR-CM) is an underdiagnosed disease and an underestimated cause of both heart failure and conduction abnormalities. It is characterized by pathologic accumulation of extracellular protein arising from unstable transthyretin (TTR) tetramers, which dissociate into monomers that misfold, aggregate, and form insoluble fibrils that are resistant to proteolysis. Cardiac amyloidosis appears in two distinct forms: hereditary and wild-type. There is considerable heterogeneity in the clinical presentation of ATTR, ranging from primarily cardiac, primarily neuropathic, or mixed cardiac and neuropathic disease. Pathogenic variants in the TTR gene that predominantly involve the heart include Val122Ile, Leu111Met, and Ile68Leu. The wild-type form of ATTR is also predominantly cardiac. Phenotypic heterogeneity is linked to differences among specific pathogenic TTR variants, geography, and the subtype of endemic versus nonendemic disease. Factors contributing to wild-type ATTR are largely unknown, but similar factors likely influence the penetrance of hereditary ATTR. Recognition of ATTR-CM is improving due to the increased use of cardiac scintigraphy as a noninvasive diagnostic tool, and early recognition of cardiac infiltration is crucial to optimize long-term prognosis.

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Section: Geneticsmentioning

confidence: 99%

ATTR Epidemiology, Genetics, and Prognostic Factors

Chukwuemeka

Mostertz

Griffin

et al. 2022

Methodist DeBakey Cardiovascular Journal

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Prevalence of Pathogenic Transthyretin Gene Variants in the Rocky Mountain Region

Jacoby,

Quan,

Todd

et al. 2024

Muscle and Nerve

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Introduction/AimsHereditary 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.MethodsColorado 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.ResultsA 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.DiscussionThe 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.

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