The TMEM43 Newfoundland mutation p.S358L causing ARVC-5 was imported from Europe and increases the stiffness of the cell nucleus
Milting H, Klauke B, Christensen AH, et al. The TMEM43 Newfoundland mutation p.S358L causing ARVC-5 was imported from Europe and increases the stiffness of the cell nucleus. European Heart Journal . 2015;36(14):872-881. AIMS: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare genetic c...
Published in: | European Heart Journal |
---|---|
Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , |
Format: | Article in Journal/Newspaper |
Language: | English |
Published: |
Oxford University Press (OUP)
2015
|
Subjects: | |
Online Access: | https://pub.uni-bielefeld.de/record/2732695 |
id |
ftubbiepub:oai:pub.uni-bielefeld.de:2732695 |
---|---|
record_format |
openpolar |
spelling |
ftubbiepub:oai:pub.uni-bielefeld.de:2732695 2023-05-15T17:19:37+02:00 The TMEM43 Newfoundland mutation p.S358L causing ARVC-5 was imported from Europe and increases the stiffness of the cell nucleus Milting, Hendrik Klauke, Bärbel Christensen, Alex Hoerby Müsebeck, Jörg Walhorn, Volker Grannemann, Sören Münnich, Tamara Šarić, Tomo Rasmussen, Torsten Bloch Jensen, Henrik Kjærulf Mogensen, Jens Baecker, Carolin Romaker, Elena Laser, Kai Thorsten zu Knyphausen, Edzard Kassner, Astrid Gummert, Jan Judge, Daniel P. Connors, Sean Hodgkinson, Kathy Young, Terry-L. van der Zwaag, Paul A. van Tintelen, J. Peter Anselmetti, Dario 2015 https://pub.uni-bielefeld.de/record/2732695 eng eng Oxford University Press (OUP) info:eu-repo/semantics/altIdentifier/doi/10.1093/eurheartj/ehu077 info:eu-repo/semantics/altIdentifier/issn/1522-9645 info:eu-repo/semantics/altIdentifier/wos/000353541400010 info:eu-repo/semantics/altIdentifier/pmid/24598986 https://pub.uni-bielefeld.de/record/2732695 info:eu-repo/semantics/closedAccess http://purl.org/coar/resource_type/c_6501 info:eu-repo/semantics/article doc-type:article text 2015 ftubbiepub https://doi.org/10.1093/eurheartj/ehu077 2022-02-08T22:34:22Z Milting H, Klauke B, Christensen AH, et al. The TMEM43 Newfoundland mutation p.S358L causing ARVC-5 was imported from Europe and increases the stiffness of the cell nucleus. European Heart Journal . 2015;36(14):872-881. AIMS: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare genetic condition caused predominantly by mutations within desmosomal genes. The mutation leading to ARVC-5 was recently identified on the island of Newfoundland and caused by the fully penetrant missense mutation p.S358L in TMEM43. Although TMEM43-p.S358L mutation carriers were also found in the USA, Germany, and Denmark, the genetic relationship between North American and European patients and the disease mechanism of this mutation remained to be clarified. METHODS AND RESULTS: We screened 22 unrelated ARVC patients without mutations in desmosomal genes and identified the TMEM43-p.S358L mutation in a German ARVC family. We excluded TMEM43-p.S358L in 22 unrelated patients with dilated cardiomyopathy. The German family shares a common haplotype with those from Newfoundland, USA, and Denmark, suggesting that the mutation originated from a common founder. Examination of 40 control chromosomes revealed an estimated age of 1300-1500 years for the mutation, which proves the European origin of the Newfoundland mutation. Skin fibroblasts from a female and two male mutation carriers were analysed in cell culture using atomic force microscopy and revealed that the cell nuclei exhibit an increased stiffness compared with TMEM43 wild-type controls. CONCLUSION: The German family is not affected by a de novo TMEM43 mutation. It is therefore expected that an unknown number of European families may be affected by the TMEM43-p.S358L founder mutation. Due to its deleterious clinical phenotype, this mutation should be checked in any case of ARVC-related genotyping. It appears that the increased stiffness of the cell nucleus might be related to the massive loss of cardiomyocytes, which is typically found in ventricles of ARVC hearts. Article in Journal/Newspaper Newfoundland PUB - Publications at Bielefeld University Christensen ENVELOPE(47.867,47.867,-67.967,-67.967) European Heart Journal 36 14 872 881 |
institution |
Open Polar |
collection |
PUB - Publications at Bielefeld University |
op_collection_id |
ftubbiepub |
language |
English |
description |
Milting H, Klauke B, Christensen AH, et al. The TMEM43 Newfoundland mutation p.S358L causing ARVC-5 was imported from Europe and increases the stiffness of the cell nucleus. European Heart Journal . 2015;36(14):872-881. AIMS: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare genetic condition caused predominantly by mutations within desmosomal genes. The mutation leading to ARVC-5 was recently identified on the island of Newfoundland and caused by the fully penetrant missense mutation p.S358L in TMEM43. Although TMEM43-p.S358L mutation carriers were also found in the USA, Germany, and Denmark, the genetic relationship between North American and European patients and the disease mechanism of this mutation remained to be clarified. METHODS AND RESULTS: We screened 22 unrelated ARVC patients without mutations in desmosomal genes and identified the TMEM43-p.S358L mutation in a German ARVC family. We excluded TMEM43-p.S358L in 22 unrelated patients with dilated cardiomyopathy. The German family shares a common haplotype with those from Newfoundland, USA, and Denmark, suggesting that the mutation originated from a common founder. Examination of 40 control chromosomes revealed an estimated age of 1300-1500 years for the mutation, which proves the European origin of the Newfoundland mutation. Skin fibroblasts from a female and two male mutation carriers were analysed in cell culture using atomic force microscopy and revealed that the cell nuclei exhibit an increased stiffness compared with TMEM43 wild-type controls. CONCLUSION: The German family is not affected by a de novo TMEM43 mutation. It is therefore expected that an unknown number of European families may be affected by the TMEM43-p.S358L founder mutation. Due to its deleterious clinical phenotype, this mutation should be checked in any case of ARVC-related genotyping. It appears that the increased stiffness of the cell nucleus might be related to the massive loss of cardiomyocytes, which is typically found in ventricles of ARVC hearts. |
format |
Article in Journal/Newspaper |
author |
Milting, Hendrik Klauke, Bärbel Christensen, Alex Hoerby Müsebeck, Jörg Walhorn, Volker Grannemann, Sören Münnich, Tamara Šarić, Tomo Rasmussen, Torsten Bloch Jensen, Henrik Kjærulf Mogensen, Jens Baecker, Carolin Romaker, Elena Laser, Kai Thorsten zu Knyphausen, Edzard Kassner, Astrid Gummert, Jan Judge, Daniel P. Connors, Sean Hodgkinson, Kathy Young, Terry-L. van der Zwaag, Paul A. van Tintelen, J. Peter Anselmetti, Dario |
spellingShingle |
Milting, Hendrik Klauke, Bärbel Christensen, Alex Hoerby Müsebeck, Jörg Walhorn, Volker Grannemann, Sören Münnich, Tamara Šarić, Tomo Rasmussen, Torsten Bloch Jensen, Henrik Kjærulf Mogensen, Jens Baecker, Carolin Romaker, Elena Laser, Kai Thorsten zu Knyphausen, Edzard Kassner, Astrid Gummert, Jan Judge, Daniel P. Connors, Sean Hodgkinson, Kathy Young, Terry-L. van der Zwaag, Paul A. van Tintelen, J. Peter Anselmetti, Dario The TMEM43 Newfoundland mutation p.S358L causing ARVC-5 was imported from Europe and increases the stiffness of the cell nucleus |
author_facet |
Milting, Hendrik Klauke, Bärbel Christensen, Alex Hoerby Müsebeck, Jörg Walhorn, Volker Grannemann, Sören Münnich, Tamara Šarić, Tomo Rasmussen, Torsten Bloch Jensen, Henrik Kjærulf Mogensen, Jens Baecker, Carolin Romaker, Elena Laser, Kai Thorsten zu Knyphausen, Edzard Kassner, Astrid Gummert, Jan Judge, Daniel P. Connors, Sean Hodgkinson, Kathy Young, Terry-L. van der Zwaag, Paul A. van Tintelen, J. Peter Anselmetti, Dario |
author_sort |
Milting, Hendrik |
title |
The TMEM43 Newfoundland mutation p.S358L causing ARVC-5 was imported from Europe and increases the stiffness of the cell nucleus |
title_short |
The TMEM43 Newfoundland mutation p.S358L causing ARVC-5 was imported from Europe and increases the stiffness of the cell nucleus |
title_full |
The TMEM43 Newfoundland mutation p.S358L causing ARVC-5 was imported from Europe and increases the stiffness of the cell nucleus |
title_fullStr |
The TMEM43 Newfoundland mutation p.S358L causing ARVC-5 was imported from Europe and increases the stiffness of the cell nucleus |
title_full_unstemmed |
The TMEM43 Newfoundland mutation p.S358L causing ARVC-5 was imported from Europe and increases the stiffness of the cell nucleus |
title_sort |
tmem43 newfoundland mutation p.s358l causing arvc-5 was imported from europe and increases the stiffness of the cell nucleus |
publisher |
Oxford University Press (OUP) |
publishDate |
2015 |
url |
https://pub.uni-bielefeld.de/record/2732695 |
long_lat |
ENVELOPE(47.867,47.867,-67.967,-67.967) |
geographic |
Christensen |
geographic_facet |
Christensen |
genre |
Newfoundland |
genre_facet |
Newfoundland |
op_relation |
info:eu-repo/semantics/altIdentifier/doi/10.1093/eurheartj/ehu077 info:eu-repo/semantics/altIdentifier/issn/1522-9645 info:eu-repo/semantics/altIdentifier/wos/000353541400010 info:eu-repo/semantics/altIdentifier/pmid/24598986 https://pub.uni-bielefeld.de/record/2732695 |
op_rights |
info:eu-repo/semantics/closedAccess |
op_doi |
https://doi.org/10.1093/eurheartj/ehu077 |
container_title |
European Heart Journal |
container_volume |
36 |
container_issue |
14 |
container_start_page |
872 |
op_container_end_page |
881 |
_version_ |
1766094398562500608 |