Dilated Cardiomyopathy 1A (DCM1A) is a specific type of dilated cardiomyopathy, which is a condition that affects the heart muscle. Dilated cardiomyopathy is characterized by the enlargement and weakening of the heart's left ventricle, the main pumping chamber. This results in the heart's reduced ability to pump blood effectively. Dilated cardiomyopathy is one of the most common causes of heart failure and the most common indication for heart transplantation worldwide, with a prevalence of 40 cases per 100.000 people. Dilated cardiomyopathy can have a genetic cause and can also originate from exposure to toxins, infections, metabolic/endocrine disturbances, autoimmunity, or the presence of neuromuscular diseases such as Duchenne.
Dilated cardiomyopathy 1A genetic testing is included in Diagnostiki Athinon Monogenic Diseases Genetic Testing along with approximetaly 100 other inherited diseases, including cystic fibrosis (71 mutations) and hereditary breast cancer (genes BRCA1 415 mutations & BRCA2 419 mutations).
Symptoms of dilated cardiomyopathy can include fatigue, shortness of breath, swelling of the legs and ankles (edema), and an irregular heartbeat. Treatment may involve medications to manage symptoms, lifestyle changes, and, in some cases, advanced therapies such as heart transplantation. It's important for individuals with a family history of dilated cardiomyopathy or related heart conditions to seek medical advice and genetic counseling.
The genetic causes of dilated cardiomyopathy are diverse and involve multiple genes that code for the sarcomere, cytoskeleton, and nuclear envelope proteins.
The nuclear lamina is a fundamental structure in cells that consists of a network of filamentous proteins that lies beneath the membrane of the nucleus and determines its shape, structure, and size. Most laminopathies, or diseases affecting nuclear lamina proteins, are caused by nonsense mutations in the LMNA gene that codes for lamin A and C proteins.
LMNA is one of the genes in the human genome with the largest number of variants recorded, associated with more than 15 different diseases. Among the variants described, there are more than 250 that can cause type 1A cardiomyopathy, representing between 5 and 10% of cases of dilated cardiomyopathy.
It is suggested that alterations in LMNA could cause mechanical defects of the lamina and nuclear fragility. More recently, it has been observed that these alterations could also affect the spatial organization of chromatin.
Since cardiomyopathy 1A (associated with the LMNA gene) follows an autosomal dominant mode of inheritance, the presence of a single copy of a pathogenic variant is sufficient for the person carrying the variant to be predisposed to develop the disease.
A genetic test of dilated cardiomyopathy 1A analyzes the 24 most frequent pathogenic mutations of the LMNA gene.
With the technique used for genetic testing, only the gene's specific mutations, which are the most important and frequent in the literature, are analyzed. However, it should be noted that there are likely other gene or chromosomal mutations in the gene to be tested, which cannot be identified with this method. Different analysis techniques can be used for these cases, such as, e.g., next-generation sequencing (NGS).
