open access

Vol 64, No 8 (2006)
Other
Published online: 2006-09-13
Submitted: 2012-12-28
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Original article
Dilated cardiomyopathy caused by LMNA mutations. Clinical and morphological studies

Zofia T. Bilińska, Nicolas Sylvius, Jacek Grzybowski, Anna Fidziańska, Ewa Michalak, Ewa Walczak, Michał Walski, Katarzyna Bieganowska, Elżbieta Szymaniak, Beata Kusmierczyk, Barbara Lubiszewska, Teresa Wagner, Frédérique Tesson, Witold Rużyłło
Kardiol Pol 2006;64(8):812-819.

open access

Vol 64, No 8 (2006)
Other
Published online: 2006-09-13
Submitted: 2012-12-28

Abstract

Background: Dilated cardiomyopathy (DCM) is familial in about 20–35% of patients. The most frequently encountered mutations associated with DCM are found in LMNA. Aim: To define the frequency of LMNA mutations in a series of consecutive DCM patients and to evaluate the phenotype of mutation carriers. Methods: We screened the 12 exons of LMNA in a series of 61 Polish patients with DCM diagnosed angiographically, as well as in two DCM families. Results: Two mutations were detected in 5 mutation carriers (D192G in one proband and Y481Stop in one proband and 3 of his offspring), which represents 3.3% (2/61) of the DCM patients. These mutations were absent from 100 controls. The D192G mutation was found in a 26-year-old patient with mild DCM and heart failure leading to death within two years after onset of symptoms. Mild conduction disease was also present. Ultrastructural analysis of the endomyocardial biopsy showed a striking alteration of nuclear morphology. This finding can explain nuclear fragility and is in agreement with the pathophysiological mechanical hypothesis of LMNA mutations. All four Y481Stop mutation-carriers were affected. Three phenotypes were found: in the proband, cardiac dysrhythmia and pacemaker requirement preceded DCM leading to heart transplantation; the proband’s 13-year old daughter had conduction disease (2nd degree A-V block) with subtle skeletal muscle involvement documented by immunofluorescence study; ventricular arrhythmia was detected in the proband’s son at the age of 11 and in the proband’s daughter at the age of 18. Serum creatine kinase was normal in all mutation carriers.

Abstract

Background: Dilated cardiomyopathy (DCM) is familial in about 20–35% of patients. The most frequently encountered mutations associated with DCM are found in LMNA. Aim: To define the frequency of LMNA mutations in a series of consecutive DCM patients and to evaluate the phenotype of mutation carriers. Methods: We screened the 12 exons of LMNA in a series of 61 Polish patients with DCM diagnosed angiographically, as well as in two DCM families. Results: Two mutations were detected in 5 mutation carriers (D192G in one proband and Y481Stop in one proband and 3 of his offspring), which represents 3.3% (2/61) of the DCM patients. These mutations were absent from 100 controls. The D192G mutation was found in a 26-year-old patient with mild DCM and heart failure leading to death within two years after onset of symptoms. Mild conduction disease was also present. Ultrastructural analysis of the endomyocardial biopsy showed a striking alteration of nuclear morphology. This finding can explain nuclear fragility and is in agreement with the pathophysiological mechanical hypothesis of LMNA mutations. All four Y481Stop mutation-carriers were affected. Three phenotypes were found: in the proband, cardiac dysrhythmia and pacemaker requirement preceded DCM leading to heart transplantation; the proband’s 13-year old daughter had conduction disease (2nd degree A-V block) with subtle skeletal muscle involvement documented by immunofluorescence study; ventricular arrhythmia was detected in the proband’s son at the age of 11 and in the proband’s daughter at the age of 18. Serum creatine kinase was normal in all mutation carriers.
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Keywords

dilated cardiomyopathy; lamins; LMNA; genetics

About this article
Title

Original article
Dilated cardiomyopathy caused by LMNA mutations. Clinical and morphological studies

Journal

Kardiologia Polska (Polish Heart Journal)

Issue

Vol 64, No 8 (2006)

Pages

812-819

Published online

2006-09-13

Bibliographic record

Kardiol Pol 2006;64(8):812-819.

Keywords

dilated cardiomyopathy
lamins
LMNA
genetics

Authors

Zofia T. Bilińska
Nicolas Sylvius
Jacek Grzybowski
Anna Fidziańska
Ewa Michalak
Ewa Walczak
Michał Walski
Katarzyna Bieganowska
Elżbieta Szymaniak
Beata Kusmierczyk
Barbara Lubiszewska
Teresa Wagner
Frédérique Tesson
Witold Rużyłło

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