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DSP p.(Thr2104Glnfs*12) variant presents variably with early onset severe arrhythmias and left ventricular cardiomyopathy
BACKGROUND: Dilated cardiomyopathy (DCM) is a condition characterized by dilatation and systolic dysfunction of the left ventricle in the absence of severe coronary artery disease or abnormal loading conditions. Mutations in the titin (TTN) and lamin A/C (LMNA) genes are the two most significant con...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6995042/ https://www.ncbi.nlm.nih.gov/pubmed/32005173 http://dx.doi.org/10.1186/s12881-020-0955-z |
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author | Heliö, Krista Kangas-Kontio, Tiia Weckström, Sini Vanninen, Sari U. M. Aalto-Setälä, Katriina Alastalo, Tero-Pekka Myllykangas, Samuel Heliö, Tiina M. Koskenvuo, Juha W. |
author_facet | Heliö, Krista Kangas-Kontio, Tiia Weckström, Sini Vanninen, Sari U. M. Aalto-Setälä, Katriina Alastalo, Tero-Pekka Myllykangas, Samuel Heliö, Tiina M. Koskenvuo, Juha W. |
author_sort | Heliö, Krista |
collection | PubMed |
description | BACKGROUND: Dilated cardiomyopathy (DCM) is a condition characterized by dilatation and systolic dysfunction of the left ventricle in the absence of severe coronary artery disease or abnormal loading conditions. Mutations in the titin (TTN) and lamin A/C (LMNA) genes are the two most significant contributors in familial DCM. Previously mutations in the desmoplakin (DSP) gene have been associated with arrhythmogenic right ventricular cardiomyopathy (ARVC) and more recently with DCM. METHODS: We describe the cardiac phenotype related to a DSP mutation which was identified in ten unrelated Finnish index patients using next-generation sequencing. Sanger sequencing was used to verify the presence of this DSP variant in the probands’ relatives. Medical records were obtained, and clinical evaluation was performed. RESULTS: We identified DSP c.6310delA, p.(Thr2104Glnfs*12) variant in 17 individuals of which 11 (65%) fulfilled the DCM diagnostic criteria. This pathogenic variant presented with left ventricular dilatation, dysfunction and major ventricular arrhythmias. Two patients showed late gadolinium enhancement (LGE) and myocardial edema on cardiac magnetic resonance imaging (MRI) that may suggest inflammatory process at myocardium. CONCLUSIONS: The patients diagnosed with DCM showed an arrhythmogenic phenotype as well as SCD at young age supporting the recently proposed concept of arrhythmogenic cardiomyopathy. This study also demonstrates relatively low penetrance of truncating DSP variant in the probands’ family members by the age of 40. Further studies are needed to elucidate the possible relations between myocardial inflammation and pathogenic DSP variants. |
format | Online Article Text |
id | pubmed-6995042 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-69950422020-02-04 DSP p.(Thr2104Glnfs*12) variant presents variably with early onset severe arrhythmias and left ventricular cardiomyopathy Heliö, Krista Kangas-Kontio, Tiia Weckström, Sini Vanninen, Sari U. M. Aalto-Setälä, Katriina Alastalo, Tero-Pekka Myllykangas, Samuel Heliö, Tiina M. Koskenvuo, Juha W. BMC Med Genet Research Article BACKGROUND: Dilated cardiomyopathy (DCM) is a condition characterized by dilatation and systolic dysfunction of the left ventricle in the absence of severe coronary artery disease or abnormal loading conditions. Mutations in the titin (TTN) and lamin A/C (LMNA) genes are the two most significant contributors in familial DCM. Previously mutations in the desmoplakin (DSP) gene have been associated with arrhythmogenic right ventricular cardiomyopathy (ARVC) and more recently with DCM. METHODS: We describe the cardiac phenotype related to a DSP mutation which was identified in ten unrelated Finnish index patients using next-generation sequencing. Sanger sequencing was used to verify the presence of this DSP variant in the probands’ relatives. Medical records were obtained, and clinical evaluation was performed. RESULTS: We identified DSP c.6310delA, p.(Thr2104Glnfs*12) variant in 17 individuals of which 11 (65%) fulfilled the DCM diagnostic criteria. This pathogenic variant presented with left ventricular dilatation, dysfunction and major ventricular arrhythmias. Two patients showed late gadolinium enhancement (LGE) and myocardial edema on cardiac magnetic resonance imaging (MRI) that may suggest inflammatory process at myocardium. CONCLUSIONS: The patients diagnosed with DCM showed an arrhythmogenic phenotype as well as SCD at young age supporting the recently proposed concept of arrhythmogenic cardiomyopathy. This study also demonstrates relatively low penetrance of truncating DSP variant in the probands’ family members by the age of 40. Further studies are needed to elucidate the possible relations between myocardial inflammation and pathogenic DSP variants. BioMed Central 2020-01-31 /pmc/articles/PMC6995042/ /pubmed/32005173 http://dx.doi.org/10.1186/s12881-020-0955-z Text en © The Author(s). 2020 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Heliö, Krista Kangas-Kontio, Tiia Weckström, Sini Vanninen, Sari U. M. Aalto-Setälä, Katriina Alastalo, Tero-Pekka Myllykangas, Samuel Heliö, Tiina M. Koskenvuo, Juha W. DSP p.(Thr2104Glnfs*12) variant presents variably with early onset severe arrhythmias and left ventricular cardiomyopathy |
title | DSP p.(Thr2104Glnfs*12) variant presents variably with early onset severe arrhythmias and left ventricular cardiomyopathy |
title_full | DSP p.(Thr2104Glnfs*12) variant presents variably with early onset severe arrhythmias and left ventricular cardiomyopathy |
title_fullStr | DSP p.(Thr2104Glnfs*12) variant presents variably with early onset severe arrhythmias and left ventricular cardiomyopathy |
title_full_unstemmed | DSP p.(Thr2104Glnfs*12) variant presents variably with early onset severe arrhythmias and left ventricular cardiomyopathy |
title_short | DSP p.(Thr2104Glnfs*12) variant presents variably with early onset severe arrhythmias and left ventricular cardiomyopathy |
title_sort | dsp p.(thr2104glnfs*12) variant presents variably with early onset severe arrhythmias and left ventricular cardiomyopathy |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6995042/ https://www.ncbi.nlm.nih.gov/pubmed/32005173 http://dx.doi.org/10.1186/s12881-020-0955-z |
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