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Variant Transthyretin Amyloidosis (ATTRv) in Hungary: First Data on Epidemiology and Clinical Features

Background: Variant transthyretin amyloidosis (ATTRv) is an autosomal dominant inherited disease, where the mutation of the transthyretin gene (TTR) results in the deposition of pathogenic protein fibrils in various tissues. The mutation type influences the clinical course. Until now, no data were a...

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Autores principales: Pozsonyi, Zoltán, Peskó, Gergely, Takács, Hedvig, Csuka, Dorottya, Nagy, Viktória, Szilágyi, Ágnes, Hategan, Lidia, Muk, Balázs, Csányi, Beáta, Nyolczas, Noémi, Dézsi, Lívia, Molnár, Judit Mária, Csillik, Anita, Révész, Katalin, Iványi, Béla, Szabó, Fruzsina, Birtalan, Krisztián, Masszi, Tamás, Arányi, Zsuzsanna, Sepp, Róbert
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8392019/
https://www.ncbi.nlm.nih.gov/pubmed/34440326
http://dx.doi.org/10.3390/genes12081152
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author Pozsonyi, Zoltán
Peskó, Gergely
Takács, Hedvig
Csuka, Dorottya
Nagy, Viktória
Szilágyi, Ágnes
Hategan, Lidia
Muk, Balázs
Csányi, Beáta
Nyolczas, Noémi
Dézsi, Lívia
Molnár, Judit Mária
Csillik, Anita
Révész, Katalin
Iványi, Béla
Szabó, Fruzsina
Birtalan, Krisztián
Masszi, Tamás
Arányi, Zsuzsanna
Sepp, Róbert
author_facet Pozsonyi, Zoltán
Peskó, Gergely
Takács, Hedvig
Csuka, Dorottya
Nagy, Viktória
Szilágyi, Ágnes
Hategan, Lidia
Muk, Balázs
Csányi, Beáta
Nyolczas, Noémi
Dézsi, Lívia
Molnár, Judit Mária
Csillik, Anita
Révész, Katalin
Iványi, Béla
Szabó, Fruzsina
Birtalan, Krisztián
Masszi, Tamás
Arányi, Zsuzsanna
Sepp, Róbert
author_sort Pozsonyi, Zoltán
collection PubMed
description Background: Variant transthyretin amyloidosis (ATTRv) is an autosomal dominant inherited disease, where the mutation of the transthyretin gene (TTR) results in the deposition of pathogenic protein fibrils in various tissues. The mutation type influences the clinical course. Until now, no data were available on the genotype, phenotype, and prevalence of Hungarian ATTRv patients. The aim of our study was to assess the prevalence, regional distribution, genotypes, and phenotypes of Hungarian patients with ATTRv. Methods: With the collaboration of Hungarian regional and university centers, we identified patients diagnosed with ATTRv. We also searched prior publications for case studies of Hungarian ATTRv patients. Results: 40 individuals in 23 families with ATTRv were identified within the borders of Hungary. At the time of the diagnosis, 24 of them were symptomatic. The two most common mutations were ATTRHis88Arg (nine families) and ATTRIle107Val (8 families). ATTRVal30Met was demonstrated in 2 families, and ATTRVal122del, ATTRPhe33Leu, ATTRIle84Ser, and ATTRAsp18Gly in one family each. The median age of the symptomatic patients at the time of clinical diagnosis was 65 years. The most common clinically significant organ involvement was restrictive cardiomyopathy, found in 24 patients. Polyneuropathy was diagnosed in 20 patients. A total of 19 patients showed a mixed phenotype. The leading symptom was heart failure in 8 cases (3 of them had only cardiac symptoms), polyneuropathy in 11 cases (all of them also had cardiac symptoms), and equally severe cardiac and neuropathy symptoms were present in 3 cases. Out of 24 symptomatic patients, 10 received targeted pharmacological therapy. The follow-up period ranged from 1 to 195 months. At the time of the retrospective analysis, 12 patients had already died, and 1 patient underwent heart transplantation. Conclusions: As TTR genotype influences the phenotype and clinical course of ATTRv, it is important to know the regional data. In Hungary, ATTRHis88Arg and ATTRIle107Val are the most common mutations in ATTRv, both presenting with mixed phenotype, but the median age at the time of the diagnosis is 9 years lower in patients with ATTRHis88Arg than in patients with ATTRIle107Val.
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spelling pubmed-83920192021-08-28 Variant Transthyretin Amyloidosis (ATTRv) in Hungary: First Data on Epidemiology and Clinical Features Pozsonyi, Zoltán Peskó, Gergely Takács, Hedvig Csuka, Dorottya Nagy, Viktória Szilágyi, Ágnes Hategan, Lidia Muk, Balázs Csányi, Beáta Nyolczas, Noémi Dézsi, Lívia Molnár, Judit Mária Csillik, Anita Révész, Katalin Iványi, Béla Szabó, Fruzsina Birtalan, Krisztián Masszi, Tamás Arányi, Zsuzsanna Sepp, Róbert Genes (Basel) Article Background: Variant transthyretin amyloidosis (ATTRv) is an autosomal dominant inherited disease, where the mutation of the transthyretin gene (TTR) results in the deposition of pathogenic protein fibrils in various tissues. The mutation type influences the clinical course. Until now, no data were available on the genotype, phenotype, and prevalence of Hungarian ATTRv patients. The aim of our study was to assess the prevalence, regional distribution, genotypes, and phenotypes of Hungarian patients with ATTRv. Methods: With the collaboration of Hungarian regional and university centers, we identified patients diagnosed with ATTRv. We also searched prior publications for case studies of Hungarian ATTRv patients. Results: 40 individuals in 23 families with ATTRv were identified within the borders of Hungary. At the time of the diagnosis, 24 of them were symptomatic. The two most common mutations were ATTRHis88Arg (nine families) and ATTRIle107Val (8 families). ATTRVal30Met was demonstrated in 2 families, and ATTRVal122del, ATTRPhe33Leu, ATTRIle84Ser, and ATTRAsp18Gly in one family each. The median age of the symptomatic patients at the time of clinical diagnosis was 65 years. The most common clinically significant organ involvement was restrictive cardiomyopathy, found in 24 patients. Polyneuropathy was diagnosed in 20 patients. A total of 19 patients showed a mixed phenotype. The leading symptom was heart failure in 8 cases (3 of them had only cardiac symptoms), polyneuropathy in 11 cases (all of them also had cardiac symptoms), and equally severe cardiac and neuropathy symptoms were present in 3 cases. Out of 24 symptomatic patients, 10 received targeted pharmacological therapy. The follow-up period ranged from 1 to 195 months. At the time of the retrospective analysis, 12 patients had already died, and 1 patient underwent heart transplantation. Conclusions: As TTR genotype influences the phenotype and clinical course of ATTRv, it is important to know the regional data. In Hungary, ATTRHis88Arg and ATTRIle107Val are the most common mutations in ATTRv, both presenting with mixed phenotype, but the median age at the time of the diagnosis is 9 years lower in patients with ATTRHis88Arg than in patients with ATTRIle107Val. MDPI 2021-07-28 /pmc/articles/PMC8392019/ /pubmed/34440326 http://dx.doi.org/10.3390/genes12081152 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Pozsonyi, Zoltán
Peskó, Gergely
Takács, Hedvig
Csuka, Dorottya
Nagy, Viktória
Szilágyi, Ágnes
Hategan, Lidia
Muk, Balázs
Csányi, Beáta
Nyolczas, Noémi
Dézsi, Lívia
Molnár, Judit Mária
Csillik, Anita
Révész, Katalin
Iványi, Béla
Szabó, Fruzsina
Birtalan, Krisztián
Masszi, Tamás
Arányi, Zsuzsanna
Sepp, Róbert
Variant Transthyretin Amyloidosis (ATTRv) in Hungary: First Data on Epidemiology and Clinical Features
title Variant Transthyretin Amyloidosis (ATTRv) in Hungary: First Data on Epidemiology and Clinical Features
title_full Variant Transthyretin Amyloidosis (ATTRv) in Hungary: First Data on Epidemiology and Clinical Features
title_fullStr Variant Transthyretin Amyloidosis (ATTRv) in Hungary: First Data on Epidemiology and Clinical Features
title_full_unstemmed Variant Transthyretin Amyloidosis (ATTRv) in Hungary: First Data on Epidemiology and Clinical Features
title_short Variant Transthyretin Amyloidosis (ATTRv) in Hungary: First Data on Epidemiology and Clinical Features
title_sort variant transthyretin amyloidosis (attrv) in hungary: first data on epidemiology and clinical features
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8392019/
https://www.ncbi.nlm.nih.gov/pubmed/34440326
http://dx.doi.org/10.3390/genes12081152
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