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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MDPI AG
2022-01-01
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| Series: | Cardiogenetics |
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| Online Access: | https://www.mdpi.com/2035-8148/12/1/1 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Torsten B. Rasmussen |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T16:19:25Z |
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| language | English |
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| series | Cardiogenetics |
| spelling | doaj.art-90f3b2b3ee204402b3fe137432d97be02022-12-21T18:20:16ZengMDPI AGCardiogenetics2035-82532035-81482022-01-0112111110.3390/cardiogenetics12010001Transthyretin Gene Variants and Associated Phenotypes in Danish Patients with Amyloid CardiomyopathyTorsten B. Rasmussen0Bertil T. Ladefoged1Anne M. Dybro2Tor S. Clemmensen3Rikke H. Sørensen4Astrid J. Terkelsen5Henning Mølgaard6Henrik Vase7Steen H. Poulsen8Department of Cardiology, Aarhus University Hospital, DK-8200 Aarhus, DenmarkDepartment of Cardiology, Aarhus University Hospital, DK-8200 Aarhus, DenmarkDepartment of Cardiology, Aarhus University Hospital, DK-8200 Aarhus, DenmarkDepartment of Cardiology, Aarhus University Hospital, DK-8200 Aarhus, DenmarkDepartment of Molecular Medicine, Aarhus University Hospital, DK-8200 Aarhus, DenmarkDepartment of Neurology, Aarhus University Hospital, DK-8200 Aarhus, DenmarkDepartment of Cardiology, Aarhus University Hospital, DK-8200 Aarhus, DenmarkDepartment of Cardiology, Aarhus University Hospital, DK-8200 Aarhus, DenmarkDepartment of Cardiology, Aarhus University Hospital, DK-8200 Aarhus, DenmarkGenotyping 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.https://www.mdpi.com/2035-8148/12/1/1transthyretinamyloidosiscardiomyopathygeneticsTTRATTRv |
| spellingShingle | 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 Transthyretin Gene Variants and Associated Phenotypes in Danish Patients with Amyloid Cardiomyopathy Cardiogenetics transthyretin amyloidosis cardiomyopathy genetics TTR ATTRv |
| title | Transthyretin Gene Variants and Associated Phenotypes in Danish Patients with Amyloid Cardiomyopathy |
| title_full | Transthyretin Gene Variants and Associated Phenotypes in Danish Patients with Amyloid Cardiomyopathy |
| title_fullStr | Transthyretin Gene Variants and Associated Phenotypes in Danish Patients with Amyloid Cardiomyopathy |
| title_full_unstemmed | Transthyretin Gene Variants and Associated Phenotypes in Danish Patients with Amyloid Cardiomyopathy |
| title_short | Transthyretin Gene Variants and Associated Phenotypes in Danish Patients with Amyloid Cardiomyopathy |
| title_sort | transthyretin gene variants and associated phenotypes in danish patients with amyloid cardiomyopathy |
| topic | transthyretin amyloidosis cardiomyopathy genetics TTR ATTRv |
| url | https://www.mdpi.com/2035-8148/12/1/1 |
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