Identification of a variant hotspot in "MYBPC3" and of a novel "CSRP3" autosomal recessive alteration in a cohort of Polish patients with hypertrophic cardiomyopathy
INTRODUCTION Hypertrophic cardiomyopathy (HCM) is a heart disorder caused by autosomal dominant alterations affecting both sarcomeric genes and other nonsarcomeric loci in a minority of cases. However, in some patients, the occurrence of the causal pathogenic variant or variants in homozygosity, com...
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ftjagiellonuniir:oai:ruj.uj.edu.pl:item/257070 2024-05-19T07:42:52+00:00 Identification of a variant hotspot in "MYBPC3" and of a novel "CSRP3" autosomal recessive alteration in a cohort of Polish patients with hypertrophic cardiomyopathy Lipari, Martina Wypasek, Ewa Karpinski, Marek Tomkiewicz-Pająk, Lidia Laino, Luigi Binni, Francesco Giannarelli, Diana Rubiś, Paweł Petkow-Dimitrow, Paweł Undas, Anetta Grammatico, Paola Bottillo, Irene 2020 https://ruj.uj.edu.pl/xmlui/handle/item/257070 https://doi.org/10.20452/pamw.15130 https://www.mp.pl/paim/issue/article/15130 eng eng Polskie Archiwum Medycyny Wewnętrznej = Polish Archives of Internal Medicine, T. 130, nr 2, s. 89-99 0032-3772 1897-9483 doi:10.20452/pamw.15130 https://ruj.uj.edu.pl/xmlui/handle/item/257070 https://www.mp.pl/paim/issue/article/15130 Udzielam licencji. Uznanie autorstwa - Użycie niekomercyjne - Na tych samych warunkach 4.0 Międzynarodowa http://creativecommons.org/licenses/by-nc-sa/4.0/legalcode.pl CSRP3 human KO hypertrophic cardiomyopathy MYBPC3 founder mutation Polish population artykuł w czasopiśmie 2020 ftjagiellonuniir https://doi.org/10.20452/pamw.15130 2024-04-19T00:07:33Z INTRODUCTION Hypertrophic cardiomyopathy (HCM) is a heart disorder caused by autosomal dominant alterations affecting both sarcomeric genes and other nonsarcomeric loci in a minority of cases. However, in some patients, the occurrence of the causal pathogenic variant or variants in homozygosity, compound heterozygosity, or double heterozygosity has also been described. Most of the HCM pathogenic variants are missense and unique, but truncating mutations of the MYBPC3 gene have been reported as founder pathogenic variants in populations from Finland, France, Japan, Iceland, Italy, and the Netherlands. OBJECTIVES This study aimed to assess the genetic background of HCM in a cohort of Polish patients. PATIENTS AND METHODS Twenty‑nine Polish patients were analyzed by a next‑generation sequencing panel including 404 cardiovascular genes. RESULTS Pathogenic variants were found in 41% of the patients, with ultra‑rare MYBPC3 c.2541C>G (p.Tyr847Ter) mutation standing for a variant hotspot and correlating with a lower age at HCM diagnosis. Among the nonsarcomeric genes, the CSRP3 mutation was found in a single case carrying the novel c.364C>T (p.Arg122Ter) variant in homozygosity. With this finding, the total number of known HCM cases with human CSRP3 knockout cases has reached 3. CONCLUSIONS This report expands the mutational spectrum and the inheritance pattern of HCM. Article in Journal/Newspaper Iceland Jagiellonian University Repository Polish Archives of Internal Medicine |
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Open Polar |
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Jagiellonian University Repository |
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ftjagiellonuniir |
language |
English |
topic |
CSRP3 human KO hypertrophic cardiomyopathy MYBPC3 founder mutation Polish population |
spellingShingle |
CSRP3 human KO hypertrophic cardiomyopathy MYBPC3 founder mutation Polish population Lipari, Martina Wypasek, Ewa Karpinski, Marek Tomkiewicz-Pająk, Lidia Laino, Luigi Binni, Francesco Giannarelli, Diana Rubiś, Paweł Petkow-Dimitrow, Paweł Undas, Anetta Grammatico, Paola Bottillo, Irene Identification of a variant hotspot in "MYBPC3" and of a novel "CSRP3" autosomal recessive alteration in a cohort of Polish patients with hypertrophic cardiomyopathy |
topic_facet |
CSRP3 human KO hypertrophic cardiomyopathy MYBPC3 founder mutation Polish population |
description |
INTRODUCTION Hypertrophic cardiomyopathy (HCM) is a heart disorder caused by autosomal dominant alterations affecting both sarcomeric genes and other nonsarcomeric loci in a minority of cases. However, in some patients, the occurrence of the causal pathogenic variant or variants in homozygosity, compound heterozygosity, or double heterozygosity has also been described. Most of the HCM pathogenic variants are missense and unique, but truncating mutations of the MYBPC3 gene have been reported as founder pathogenic variants in populations from Finland, France, Japan, Iceland, Italy, and the Netherlands. OBJECTIVES This study aimed to assess the genetic background of HCM in a cohort of Polish patients. PATIENTS AND METHODS Twenty‑nine Polish patients were analyzed by a next‑generation sequencing panel including 404 cardiovascular genes. RESULTS Pathogenic variants were found in 41% of the patients, with ultra‑rare MYBPC3 c.2541C>G (p.Tyr847Ter) mutation standing for a variant hotspot and correlating with a lower age at HCM diagnosis. Among the nonsarcomeric genes, the CSRP3 mutation was found in a single case carrying the novel c.364C>T (p.Arg122Ter) variant in homozygosity. With this finding, the total number of known HCM cases with human CSRP3 knockout cases has reached 3. CONCLUSIONS This report expands the mutational spectrum and the inheritance pattern of HCM. |
format |
Article in Journal/Newspaper |
author |
Lipari, Martina Wypasek, Ewa Karpinski, Marek Tomkiewicz-Pająk, Lidia Laino, Luigi Binni, Francesco Giannarelli, Diana Rubiś, Paweł Petkow-Dimitrow, Paweł Undas, Anetta Grammatico, Paola Bottillo, Irene |
author_facet |
Lipari, Martina Wypasek, Ewa Karpinski, Marek Tomkiewicz-Pająk, Lidia Laino, Luigi Binni, Francesco Giannarelli, Diana Rubiś, Paweł Petkow-Dimitrow, Paweł Undas, Anetta Grammatico, Paola Bottillo, Irene |
author_sort |
Lipari, Martina |
title |
Identification of a variant hotspot in "MYBPC3" and of a novel "CSRP3" autosomal recessive alteration in a cohort of Polish patients with hypertrophic cardiomyopathy |
title_short |
Identification of a variant hotspot in "MYBPC3" and of a novel "CSRP3" autosomal recessive alteration in a cohort of Polish patients with hypertrophic cardiomyopathy |
title_full |
Identification of a variant hotspot in "MYBPC3" and of a novel "CSRP3" autosomal recessive alteration in a cohort of Polish patients with hypertrophic cardiomyopathy |
title_fullStr |
Identification of a variant hotspot in "MYBPC3" and of a novel "CSRP3" autosomal recessive alteration in a cohort of Polish patients with hypertrophic cardiomyopathy |
title_full_unstemmed |
Identification of a variant hotspot in "MYBPC3" and of a novel "CSRP3" autosomal recessive alteration in a cohort of Polish patients with hypertrophic cardiomyopathy |
title_sort |
identification of a variant hotspot in "mybpc3" and of a novel "csrp3" autosomal recessive alteration in a cohort of polish patients with hypertrophic cardiomyopathy |
publishDate |
2020 |
url |
https://ruj.uj.edu.pl/xmlui/handle/item/257070 https://doi.org/10.20452/pamw.15130 https://www.mp.pl/paim/issue/article/15130 |
genre |
Iceland |
genre_facet |
Iceland |
op_relation |
Polskie Archiwum Medycyny Wewnętrznej = Polish Archives of Internal Medicine, T. 130, nr 2, s. 89-99 0032-3772 1897-9483 doi:10.20452/pamw.15130 https://ruj.uj.edu.pl/xmlui/handle/item/257070 https://www.mp.pl/paim/issue/article/15130 |
op_rights |
Udzielam licencji. Uznanie autorstwa - Użycie niekomercyjne - Na tych samych warunkach 4.0 Międzynarodowa http://creativecommons.org/licenses/by-nc-sa/4.0/legalcode.pl |
op_doi |
https://doi.org/10.20452/pamw.15130 |
container_title |
Polish Archives of Internal Medicine |
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1799482565646614528 |