Transthyretin Gene Variants and Associated Phenotypes in Danish Patients with Amyloid Cardiomyopathy

Transthyretin Gene Variants and Associated Phenotypes in Danish Patients with Amyloid Cardiomyopathy

Genotyping divides transthyretin cardiac amyloidosis (ATTR-CA) in hereditary (ATTRv) and wild type (ATTRwt) forms. This study investigated the prevalence and clinical presentation of ATTRv in a contemporary cohort of consecutive ATTR-CA patients diagnosed at a tertiary Danish amyloidosis center. Age...

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Bibliographic Details
Main Authors: Torsten B. Rasmussen, Bertil T. Ladefoged, Anne M. Dybro, Tor S. Clemmensen, Rikke H. Sørensen, Astrid J. Terkelsen, Henning Mølgaard, Henrik Vase, Steen H. Poulsen
Format: Article
Language:English
Published: MDPI AG 2022-01-01
Series:Cardiogenetics
Subjects:
transthyretin
amyloidosis
cardiomyopathy
genetics
TTR
ATTRv
Online Access:https://www.mdpi.com/2035-8148/12/1/1
Description
Summary:Genotyping divides transthyretin cardiac amyloidosis (ATTR-CA) in hereditary (ATTRv) and wild type (ATTRwt) forms. This study investigated the prevalence and clinical presentation of ATTRv in a contemporary cohort of consecutive ATTR-CA patients diagnosed at a tertiary Danish amyloidosis center. Age at diagnosis, clinical- and echocardiographic data, and transthyretin (TTR) genotype were recorded. Relatives of ATTRv patients underwent clinical phenotyping and predictive gene testing. Genetic testing in 102 patients identified four TTR variant carriers: p.Pro63Ser, p.Ala65Ser (<i>n</i> = 2) and p.Val142Ile. The mean age of ATTRv index patients was significantly lower compared to ATTRwt patients: 70.2 ± 1.2 versus 80.0 ± 6.2, <i>p</i>-value: 0.005. Evaluation of ATTRv families identified seven TTR variant carriers with a median age of 65 years (range 48–76) and three were diagnosed with ATTR-CA by DPD-scintigraphy. Family members with ATTR-CA were all asymptomatic and had normal levels of cardiac biomarkers. In conclusion, the prevalence of ATTRv in a contemporary Danish ATTR-CA cohort is 4%. ATTRv index patients were significantly younger age at diagnosis than ATTRwt patients. Non-p.Leu131Met TTR variants have reduced penetrance at the age of 65 years in which approximately half of variant carriers have asymptomatic ATTR-CA with normal LV systolic function and cardiac biomarker analyses.
ISSN:2035-8253
2035-8148

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