Phenotypic Characteristic of LMNA Associated Dilated Cardiomyopathy



Tatiyana Vaikhanskaya1, Larisa Sivitskaya2, Nina Danilenko2, Tatsiyana Kurushka1
1 Medical Information Technology, Republican Scientific and Practical Center "Cardiology", Belarus
2 Cytoplasmic Inheritance, Institute of Genetics and Cytology, Belarus

Dilated cardiomyopathy (DCM) caused by mutations in the lamin A/C (LMNA) gene is often associated with conduction disorders, cardiac arrhythmias and high risk of sudden cardiac death (SCD).

The purpose of this study was to identify LMNA gene mutations, estimate their frequency in patients (pts) with sporadic DCM and phenotypic-genotypic analysis.

Methods: We enrolled 189 pts with sporadic DCM;of these, 92 (48,6%) pts who had a primary manifestation of conduction disorders and cardiac arrhythmias (aged 42,3±11,7; men 89,1%; NYHA class 2,7±0,4; LV EF 25,9±11,1%; LBBB 43.5%; 1-3 d AV block 21,7%; sVT/nsVT 64,1%; AF 34,8%)genetic analysis of LMNA was performed by SSCP and sequencing.

Results: In 28 (30,4%) pts with DCM were identified changes in gene LMNA: replacement c.1698 * C>T in exon 10 in 23 pts; missense mutations in exon 3 - с.612G>A and c.569G>C in 2 pts; missense mutations c.1247S>T in the 9th exon and c.150S>T exon 1; in addition, 2 pts were identified as carriers simultaneously three nucleotide changes: 5 exon - c.639+73C>T and c.639+56G>A, and c.861T>C located intron. Clinical and morpho-functional parameters were included in correlative and dispersive univariate analysis. As a result, LMNA changes were associated with a positive mTWA (p <0.005), ↑CK levels (p <0.01), nsVT (p <0.05), 1-3d AV block (p <0.01) and LVGS mean (p <0.05). By univariate analysis pramathers of LVGS mean and nsVT lost significance (F = 2,95; p = 0.056), while positive test mTWA (F = 9,6; p = 0,000), ↑CK levels (F = 6,43; p = 0.015), and 1-3d AV block (F = 5,7; p = 0.019) have confirmed their predictive accuracy.

Conclusion: Thus, 30,4% DCM developed a phenotype with arrhythmic and conduction disorders caused by LMNA changes. Since the high risk of SCD associated with LMNA-related DCM, revealing of phenotypic findings as ↑CK levels, AV blockade and positive test mTWA will allow to select a group of sporadic DCM for obligatory genetic screening in order timely to determine an optimal management.