Lamin A/C mutation affecting primarily the right side of the heart

Laura Ollila, Johanna Kuusisto, Keijo Peuhkurinen, Satu Kärkkäinen, Petri Tuomainen, Maija Kaartinen, Olayinka Raheem, Bjarne Udd, Jarkko Magga, Janne Rapola, Annukka Lahtinen, Eero Lehtonen, Miia Holmström, Sari Marjut Kivistö, Elisabeth Widén, Markku Saksa, Tiina Heliö

Research output: Contribution to journalArticleScientificpeer-review

Abstract

LMNA mutations are amongst the most important causes of familial dilated cardiomyopathy. The most important cause of arrhythmogenic right ventricular cardiomyopathy (ARVC) is desmosomal pathology. The aim of the study was to elucidate the role of LMNA mutations among Finnish cardiomyopathy patients. We screened 135 unrelated cardiomyopathy patients for LMNA mutations. Because of unusual phenotype, two patients were screened for the known Finnish ARVC-related mutations of desmosomal genes, and their Plakophilin-2b gene was sequenced. Myocardial samples from two patients were examined by immunohistochemical plakoglobin staining and in one case by electron microscopy. We found a new LMNA mutation Phe237Ser in a family of five affected members with a cardiomyopathy affecting primarily the right side of the heart. The phenotype resembles ARVC but does not fulfill the Task Force Criteria. The main clinical manifestations of the mutation were severe tricuspid insufficiency, right ventricular enlargement and failure. Three of the affected patients died of the heart disease, and the two living patients received heart transplants at ages 44 and 47. Electron microscopy showed nuclear blebbing compatible with laminopathy. Immunohisto - chemical analysis did not suggest desmosomal pathology. No desmosomal mutations were found. The Phe237Ser LMNA mutation causes a phenotype different from traditional cardiolaminopathy. Our findings suggest that cardiomyopathy affecting primarily the right side of the heart is not always caused by desmosomal pathology. Our observations highlight the challenges in classifying cardiomyopathies, as there often is significant overlap between the traditional categories.
Original languageEnglish
JournalCardiogenetics
Volume3
Issue number1
Pages (from-to)1
Number of pages1
ISSN2035-8148
DOIs
Publication statusPublished - 2013
MoE publication typeA1 Journal article-refereed

Fields of Science

  • LMNA, Lamin A/C, dilated cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy.
  • 3121 Internal medicine

Cite this

Ollila, Laura ; Kuusisto, Johanna ; Peuhkurinen, Keijo ; Kärkkäinen, Satu ; Tuomainen, Petri ; Kaartinen, Maija ; Raheem, Olayinka ; Udd, Bjarne ; Magga, Jarkko ; Rapola, Janne ; Lahtinen, Annukka ; Lehtonen, Eero ; Holmström, Miia ; Kivistö, Sari Marjut ; Widén, Elisabeth ; Saksa, Markku ; Heliö, Tiina. / Lamin A/C mutation affecting primarily the right side of the heart. In: Cardiogenetics. 2013 ; Vol. 3, No. 1. pp. 1.
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abstract = "LMNA mutations are amongst the most important causes of familial dilated cardiomyopathy. The most important cause of arrhythmogenic right ventricular cardiomyopathy (ARVC) is desmosomal pathology. The aim of the study was to elucidate the role of LMNA mutations among Finnish cardiomyopathy patients. We screened 135 unrelated cardiomyopathy patients for LMNA mutations. Because of unusual phenotype, two patients were screened for the known Finnish ARVC-related mutations of desmosomal genes, and their Plakophilin-2b gene was sequenced. Myocardial samples from two patients were examined by immunohistochemical plakoglobin staining and in one case by electron microscopy. We found a new LMNA mutation Phe237Ser in a family of five affected members with a cardiomyopathy affecting primarily the right side of the heart. The phenotype resembles ARVC but does not fulfill the Task Force Criteria. The main clinical manifestations of the mutation were severe tricuspid insufficiency, right ventricular enlargement and failure. Three of the affected patients died of the heart disease, and the two living patients received heart transplants at ages 44 and 47. Electron microscopy showed nuclear blebbing compatible with laminopathy. Immunohisto - chemical analysis did not suggest desmosomal pathology. No desmosomal mutations were found. The Phe237Ser LMNA mutation causes a phenotype different from traditional cardiolaminopathy. Our findings suggest that cardiomyopathy affecting primarily the right side of the heart is not always caused by desmosomal pathology. Our observations highlight the challenges in classifying cardiomyopathies, as there often is significant overlap between the traditional categories.",
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author = "Laura Ollila and Johanna Kuusisto and Keijo Peuhkurinen and Satu K{\"a}rkk{\"a}inen and Petri Tuomainen and Maija Kaartinen and Olayinka Raheem and Bjarne Udd and Jarkko Magga and Janne Rapola and Annukka Lahtinen and Eero Lehtonen and Miia Holmstr{\"o}m and Kivist{\"o}, {Sari Marjut} and Elisabeth Wid{\'e}n and Markku Saksa and Tiina Heli{\"o}",
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Lamin A/C mutation affecting primarily the right side of the heart. / Ollila, Laura; Kuusisto, Johanna; Peuhkurinen, Keijo; Kärkkäinen, Satu; Tuomainen, Petri; Kaartinen, Maija; Raheem, Olayinka; Udd, Bjarne; Magga, Jarkko; Rapola, Janne; Lahtinen, Annukka; Lehtonen, Eero; Holmström, Miia; Kivistö, Sari Marjut; Widén, Elisabeth; Saksa, Markku; Heliö, Tiina.

In: Cardiogenetics, Vol. 3, No. 1, 2013, p. 1.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Lamin A/C mutation affecting primarily the right side of the heart

AU - Ollila, Laura

AU - Kuusisto, Johanna

AU - Peuhkurinen, Keijo

AU - Kärkkäinen, Satu

AU - Tuomainen, Petri

AU - Kaartinen, Maija

AU - Raheem, Olayinka

AU - Udd, Bjarne

AU - Magga, Jarkko

AU - Rapola, Janne

AU - Lahtinen, Annukka

AU - Lehtonen, Eero

AU - Holmström, Miia

AU - Kivistö, Sari Marjut

AU - Widén, Elisabeth

AU - Saksa, Markku

AU - Heliö, Tiina

PY - 2013

Y1 - 2013

N2 - LMNA mutations are amongst the most important causes of familial dilated cardiomyopathy. The most important cause of arrhythmogenic right ventricular cardiomyopathy (ARVC) is desmosomal pathology. The aim of the study was to elucidate the role of LMNA mutations among Finnish cardiomyopathy patients. We screened 135 unrelated cardiomyopathy patients for LMNA mutations. Because of unusual phenotype, two patients were screened for the known Finnish ARVC-related mutations of desmosomal genes, and their Plakophilin-2b gene was sequenced. Myocardial samples from two patients were examined by immunohistochemical plakoglobin staining and in one case by electron microscopy. We found a new LMNA mutation Phe237Ser in a family of five affected members with a cardiomyopathy affecting primarily the right side of the heart. The phenotype resembles ARVC but does not fulfill the Task Force Criteria. The main clinical manifestations of the mutation were severe tricuspid insufficiency, right ventricular enlargement and failure. Three of the affected patients died of the heart disease, and the two living patients received heart transplants at ages 44 and 47. Electron microscopy showed nuclear blebbing compatible with laminopathy. Immunohisto - chemical analysis did not suggest desmosomal pathology. No desmosomal mutations were found. The Phe237Ser LMNA mutation causes a phenotype different from traditional cardiolaminopathy. Our findings suggest that cardiomyopathy affecting primarily the right side of the heart is not always caused by desmosomal pathology. Our observations highlight the challenges in classifying cardiomyopathies, as there often is significant overlap between the traditional categories.

AB - LMNA mutations are amongst the most important causes of familial dilated cardiomyopathy. The most important cause of arrhythmogenic right ventricular cardiomyopathy (ARVC) is desmosomal pathology. The aim of the study was to elucidate the role of LMNA mutations among Finnish cardiomyopathy patients. We screened 135 unrelated cardiomyopathy patients for LMNA mutations. Because of unusual phenotype, two patients were screened for the known Finnish ARVC-related mutations of desmosomal genes, and their Plakophilin-2b gene was sequenced. Myocardial samples from two patients were examined by immunohistochemical plakoglobin staining and in one case by electron microscopy. We found a new LMNA mutation Phe237Ser in a family of five affected members with a cardiomyopathy affecting primarily the right side of the heart. The phenotype resembles ARVC but does not fulfill the Task Force Criteria. The main clinical manifestations of the mutation were severe tricuspid insufficiency, right ventricular enlargement and failure. Three of the affected patients died of the heart disease, and the two living patients received heart transplants at ages 44 and 47. Electron microscopy showed nuclear blebbing compatible with laminopathy. Immunohisto - chemical analysis did not suggest desmosomal pathology. No desmosomal mutations were found. The Phe237Ser LMNA mutation causes a phenotype different from traditional cardiolaminopathy. Our findings suggest that cardiomyopathy affecting primarily the right side of the heart is not always caused by desmosomal pathology. Our observations highlight the challenges in classifying cardiomyopathies, as there often is significant overlap between the traditional categories.

KW - LMNA, Lamin A/C, dilated cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy.

KW - 3121 Internal medicine

U2 - 10.4081/cardiogenetics.2013.e1

DO - 10.4081/cardiogenetics.2013.e1

M3 - Article

VL - 3

SP - 1

JO - Cardiogenetics

JF - Cardiogenetics

SN - 2035-8253

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ER -