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Cardiac effects of the c.1583 C→G LMNA mutation in two families with Emery-Dreifuss muscular dystrophy.

Zhang L, Shen H, Zhao Z, Bing Q, Hu J - Mol Med Rep (2015)

Bottom Line: The three affected individuals exhibited a heterozygous missense mutation in the LMNA gene (c.1583 C→G), which caused a T528R amino acid change in the LMNA protein.In conclusion, the present study identified three patients with EDMD, exhibiting the same dominant LMNA mutation and presenting with a spectrum of severe cardiac abnormalities, including cardiac conduction system defects, cardiomyopathy and heart failure.As LMNA mutations have been associated with at least six clinical disorders, including EDMD, the results of the present study provide additional mutational and functional data, which may assist in further establishing LMNA mutational variation and disease pathogenesis.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiovascular Disorders, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China.

ABSTRACT
The present study aimed to examine and analyze cardiac involvement in two Emery‑Dreifuss muscular dystrophy (EDMD) pedigrees caused by the c.1583 C→G mutation of the lamin A/C gene (LMNA). The clinical and genetic characteristics of members of two families with EDMD were evaluated by performing neurological examinations, skeletal muscle biopsies, cardiac evaluations, including electrocardiography, 24 h Holter, ultrasound cardiography and 99TcM‑MIBI‑gated myocardiac perfusion imaging, and genomic DNA sequencing. Family history investigations revealed an autosomal dominant transmission pattern of the disease in Family 1 and a sporadic case in Family 2. The three affected patients exhibited typical clinical features of EDMD, including joint contractures, muscle weakness and cardiac involvement. Muscle histopathological investigation revealed dystrophic features. In addition, each affected individual exhibited either cardiac arrhythmia, which was evident as sinus tachycardia, atrial flutter or complete atrioventricular inhibition. Cardiac imaging revealed dilated cardiomyopathy in two of the individuals, one of whom was presented with heart failure. The second patient presented with no significant abnormalities in cardiac structure or function. The three affected individuals exhibited a heterozygous missense mutation in the LMNA gene (c.1583 C→G), which caused a T528R amino acid change in the LMNA protein. In conclusion, the present study identified three patients with EDMD, exhibiting the same dominant LMNA mutation and presenting with a spectrum of severe cardiac abnormalities, including cardiac conduction system defects, cardiomyopathy and heart failure. As LMNA mutations have been associated with at least six clinical disorders, including EDMD, the results of the present study provide additional mutational and functional data, which may assist in further establishing LMNA mutational variation and disease pathogenesis.

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99TcM-MIBI-gated myocardiac perfusion imaging of patients 1, 2 and 3. Patient 1 exhibited variegated changes in the left ventricular myocardium. Myocardial perfusion imaging was normal for Patient 2. Patient 3 exhibited decreased myocardial perfusion in the left ventricular apex.
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f5-mmr-12-04-5065: 99TcM-MIBI-gated myocardiac perfusion imaging of patients 1, 2 and 3. Patient 1 exhibited variegated changes in the left ventricular myocardium. Myocardial perfusion imaging was normal for Patient 2. Patient 3 exhibited decreased myocardial perfusion in the left ventricular apex.

Mentions: Further cardiac assessments revealed a variety of abnormalities in each patient (Figs. 4 and 5). The ECG and Holter of Patient 1 demonstrated complete atrioventricular inhibition and premature ventricular contractions of 26 beats/24 h. The UCG revealed that this individual had generalized cardiac enlargement, mitral and tricuspid valve regurgitation and decreased function of the left ventricle (Table II). The 99TcM-MIBI GPI assessment indicated left ventricular hypertrophy and variegated changes in the left ventricular myocardium. Patient 2 suffered from sinus tachycardia, as determined by ECG and Holter. The UCG and 99TcM-MIBI GPI scan was normal. The ECG and Holter of Patient 3 revealed atrial flutter and the UCG demonstrated mild left ventricular enlargement and decreased diastolic function of the left ventricle (Table II). The 99TcM-MIBI GPI assessment revealed that myocardial perfusion was moderately decreased in the apex of the left ventricle.


Cardiac effects of the c.1583 C→G LMNA mutation in two families with Emery-Dreifuss muscular dystrophy.

Zhang L, Shen H, Zhao Z, Bing Q, Hu J - Mol Med Rep (2015)

99TcM-MIBI-gated myocardiac perfusion imaging of patients 1, 2 and 3. Patient 1 exhibited variegated changes in the left ventricular myocardium. Myocardial perfusion imaging was normal for Patient 2. Patient 3 exhibited decreased myocardial perfusion in the left ventricular apex.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4581790&req=5

f5-mmr-12-04-5065: 99TcM-MIBI-gated myocardiac perfusion imaging of patients 1, 2 and 3. Patient 1 exhibited variegated changes in the left ventricular myocardium. Myocardial perfusion imaging was normal for Patient 2. Patient 3 exhibited decreased myocardial perfusion in the left ventricular apex.
Mentions: Further cardiac assessments revealed a variety of abnormalities in each patient (Figs. 4 and 5). The ECG and Holter of Patient 1 demonstrated complete atrioventricular inhibition and premature ventricular contractions of 26 beats/24 h. The UCG revealed that this individual had generalized cardiac enlargement, mitral and tricuspid valve regurgitation and decreased function of the left ventricle (Table II). The 99TcM-MIBI GPI assessment indicated left ventricular hypertrophy and variegated changes in the left ventricular myocardium. Patient 2 suffered from sinus tachycardia, as determined by ECG and Holter. The UCG and 99TcM-MIBI GPI scan was normal. The ECG and Holter of Patient 3 revealed atrial flutter and the UCG demonstrated mild left ventricular enlargement and decreased diastolic function of the left ventricle (Table II). The 99TcM-MIBI GPI assessment revealed that myocardial perfusion was moderately decreased in the apex of the left ventricle.

Bottom Line: The three affected individuals exhibited a heterozygous missense mutation in the LMNA gene (c.1583 C→G), which caused a T528R amino acid change in the LMNA protein.In conclusion, the present study identified three patients with EDMD, exhibiting the same dominant LMNA mutation and presenting with a spectrum of severe cardiac abnormalities, including cardiac conduction system defects, cardiomyopathy and heart failure.As LMNA mutations have been associated with at least six clinical disorders, including EDMD, the results of the present study provide additional mutational and functional data, which may assist in further establishing LMNA mutational variation and disease pathogenesis.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiovascular Disorders, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China.

ABSTRACT
The present study aimed to examine and analyze cardiac involvement in two Emery‑Dreifuss muscular dystrophy (EDMD) pedigrees caused by the c.1583 C→G mutation of the lamin A/C gene (LMNA). The clinical and genetic characteristics of members of two families with EDMD were evaluated by performing neurological examinations, skeletal muscle biopsies, cardiac evaluations, including electrocardiography, 24 h Holter, ultrasound cardiography and 99TcM‑MIBI‑gated myocardiac perfusion imaging, and genomic DNA sequencing. Family history investigations revealed an autosomal dominant transmission pattern of the disease in Family 1 and a sporadic case in Family 2. The three affected patients exhibited typical clinical features of EDMD, including joint contractures, muscle weakness and cardiac involvement. Muscle histopathological investigation revealed dystrophic features. In addition, each affected individual exhibited either cardiac arrhythmia, which was evident as sinus tachycardia, atrial flutter or complete atrioventricular inhibition. Cardiac imaging revealed dilated cardiomyopathy in two of the individuals, one of whom was presented with heart failure. The second patient presented with no significant abnormalities in cardiac structure or function. The three affected individuals exhibited a heterozygous missense mutation in the LMNA gene (c.1583 C→G), which caused a T528R amino acid change in the LMNA protein. In conclusion, the present study identified three patients with EDMD, exhibiting the same dominant LMNA mutation and presenting with a spectrum of severe cardiac abnormalities, including cardiac conduction system defects, cardiomyopathy and heart failure. As LMNA mutations have been associated with at least six clinical disorders, including EDMD, the results of the present study provide additional mutational and functional data, which may assist in further establishing LMNA mutational variation and disease pathogenesis.

Show MeSH
Related in: MedlinePlus