What is LMNA cardiomyopathy?
LMNA-related dilated cardiomyopathy (DCM) is caused by pathogenic variants in LMNA and is characterized by left ventricular enlargement and/or reduced systolic function preceded or accompanied by significant conduction system disease and/or arrhythmias.
What is a LMNA gene?
The LMNA gene provides instructions for making several slightly different proteins called lamins. The two major proteins produced from this gene, lamin A and lamin C, are made in most of the body’s cells. These proteins are made up of a nearly identical sequence of protein building blocks (amino acids).
Where is LMNA gene located?
The LMNA gene located on chromosome 1q11-q23 encodes the intermediate filament proteins lamins A and C. The lamins are located in the nuclear lamina at the nucleoplasmic side of the inner nuclear membrane and have a structural role in maintaining membrane integrity.
What is the most common genetic cardiomyopathy?
Hypertrophic Cardiomyopathy. HCM is the most common inherited cardiac disease, with a prevalence of approximately 1 in 500, and it forms a paradigm for genetics in cardiomyopathy.
How is Laminopathy diagnosed?
Diagnosis. Diagnosis is based on suggestive clinical features, the cardiac manifestations, as well as the presence of contractures and an autosomal-dominant hereditary pattern.
What family of proteins does the LMNA gene belong to?
lamin family
LMNA, also known as Lamin A/C is a protein that in humans is encoded by the LMNA gene. Lamin A/C belongs to the lamin family of proteins.
How many exons does LMNA?
12 exons
The LMNA gene has 12 exons. The gene measures 57.6 kb. Lamin C is derived from the LMNA gene using an alternative splice site located in intron 10; Lamin C thus differs C-terminally from the lamin A.
What is the prognosis for dilated cardiomyopathy?
Dilated cardiomyopathy is associated with a survival rate of less than 50% at 10 years. With better supportive care, however, improved 5- and 10-year survival rates have been reported. Peripartum cardiomyopathy may be reversible in up to 50% of patients but often recurs with subsequent pregnancy.
Are there any new treatments for LMNA-related cardiomyopathy?
LMNA-related cardiomyopathy is the focus of active in vitro and in vivo research, which is expected to generate novel biomarkers and identify new therapeutic targets. LMNA-related cardiomyopathy trials are currently underway.
Can A lamin A / C mutation cause heart failure?
Lamin A/C mutations in dilated cardiomyopathy Dilated cardiomyopathy (DCM) is one of the leading causes of heart failure and heart transplant. Mutations in 60 genes have been associated with DCM. Approximately 6% of all DCM cases are caused by mutations in the lamin A/C gene (LMNA).
How is LMNA related to cardiomyopathy in mice?
Today, the understanding of the mechanism of LMNA -related cardiac disease is largely incomplete, with numerous mouse models 10 and few studies with induced Pluripotent Stem Cells lines carrying an LMNA variants, which in one case demonstrate an effect on cellular senescence mediated by Extracellular Signal-regulated Kinase1/2 pathway. 11
What are the phenotypes of lamin A / C cardiomyopathy?
A positive cardiac phenotype was defined as the presence of atrioventricular (AV) block, atrial fibrillation/flutter (AF), ventricular tachycardia (VT), and/or echocardiographic DCM. Heart transplantation was recorded and compared with non-ischaemic DCM of other origin. Of 561 unrelated familial DCM probands, 35 (6.2%) had an LMNA mutation.
