Dilated cardiomyopathy family (Familial dilated cardiomyopathy) - Genes TTN , ABCC9 , ACTC1 , ACTN2 , ANKRD1 , BAG3 , CRYAB , CSRP3 , DES , DMD , DSG2 , EYA4 , GATAD1 , LAMA4 , LDB3 , LMNA , MYBPC3 , MYH6 , MYH7 , MYPN , PLN , PSEN1 , PSEN2 , RBM20 , SCN5A , SGCD , TAZ , TCAP , TMPO , TNNC1 , TNNI3 , TNNT2 , TPM1 and VCL
Familial dilated cardiomyopathy (FDC) is a genetic form of heart disease. It occurs when the heart muscle is dilated at least one cardiac chamber, causing the cavity to widen. As a result, the heart is unable to pump blood efficiently. Finally, the four heart chambers widen because the heart muscle is to increase the amount of blood pumped through the heart. As the heart muscle becomes thinner and weaker each time, it is less efficient to pump blood. Over time, this condition leads to heart failure.
Usually the signs and symptoms of the disease takes several years to manifest. Often these signs begin in mid-adulthood, but can occur at any time from childhood to late adulthood. Signs and symptoms of familial dilated cardiomyopathy may include arrhythmia, dyspnea, fatigue, syncope and swelling of the legs and feet. In some cases, the first sign of the disease is sudden cardiac death. The severity of the disease varies among affected individuals, even among members of the same family.
Mutations have been identified in more than 30 genes that can lead to the development of dilated cardiomyopathy family, among which are included:
- TTN (Titin),
- ABCC9 (ATP binding cassette subfamily C member 9), 12p12.1.
- ACTC1 (Actin, alpha, cardiac muscle 1), 15q14.
- ACTN2 (actinin alpha 2),
- ANKRD1 (ankyrin repeat domain 1), 10q23.31.
- BAG3 (BCL2 associated athanogene 3), 10q26.11.
- CRYAB (Alpha crystallin B), 11q23.1.
- CSRP3 (Cysteine and glycine rich protein 3), 11p15.1.
- DES (desmin)
- DMD (dystrophin),
- DSG2 (desmoglein 2),
- EYA4 (EYA transcriptional coactivator and phosphatase 4), 6q23.2.
- GATAD1 (GATA zinc finger domain containing 1), 7q21.2.
- LAMA4 (laminin alpha subunit 4),
- LDB3 (LIM domain binding 3), 10q23.2.
- LMNA (Lamin A / C),
- MYBPC3 (Myosin binding protein C, cardiac), 11p11.2.
- MYH6 (Myosin heavy chain 6), 14q11.2.
- MYH7 (Myosin heavy chain 7),
- MYPN (myopalladin),
- PLN (Phospholamban),
- PSEN1 (presenilin 1),
- PSEN2 (Presenilin 2),
- RBM20 (RNA binding motif protein 20),
- SCN5A (Sodium voltage-gated channel alpha subunit 5)
- SGCD (delta sarcoglycan),
- TAZ (tafazzin),
- TCAP (titin-cap),
- TMPO (thymopoietin),
- TNNC1 (C1 troponin, slow skeletal and cardiac type)
- TNNI3 (I3 troponin, cardiac type),
- TNNT2 (Troponin T2, cardiac type),
- TPM1 (tropomyosin 1 (alpha)),
- VCL (vinculin),
These genes encode proteins found in cardiomyocytes. Many of these proteins play important roles in heart muscle contraction through its association with sarcomere. Many other proteins associated with dilated cardiomyopathy family constitute the cytoskeleton of cardiomyocytes. The remaining proteins perform different functions within cardiomyocytes to ensure proper operation.
Mutations in the gene TTN (Titin), located on the long arm of chromosome 2 (2q31), representing approximately 20% of cases of dilated cardiomyopathy family. The TTN gene encodes titin protein, found in many sarcomeres muscle cell types, including cardiomyocytes. This protein has several functions within the sarcomeres. One of its most important tasks is to provide structure, flexibility and stability to the sarcomeres. In addition, it also plays a role in chemical signaling and the formation of new sarcomeres.
They have identified more than 40 mutations in the gene TTN result familiar dilated cardiomyopathy. These mutations lead to an abnormally short coding protein titin. It is unclear how the altered protein leads to dilated cardiomyopathy familiar, but it is likely to alter the function of the sarcomere and chemical signaling. Changes in sarcomere function reduces the heart's ability to contract, weakening and causes a thinning of the heart muscle, leading to signs and symptoms of the disease.
It is unclear how mutations in other genes lead to the development of family dilated cardiomyopathy. It is likely that changes affect the function of cardiomyocytes and reduce the ability of these cells to shrink, weaken and refine the heart muscle.
Dilated cardiomyopathy has the familiar different inheritance patterns depending on the gene involved. Between 80% and 90% of cases, the disease is inherited as an autosomal dominant, which means that a copy of the altered gene in each cell is sufficient to express the alteration. In most cases, an affected person inherits the mutation from an affected parent. However, some people who inherit the altered gene never develop disease characteristics (reduced penetrance). Other cases are due to new mutations in the gene and occur in people with no history of disease in your family. In rare cases, the disease is inherited in an autosomal recessive pattern, which means that both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease. In other rare cases, dilated cardiomyopathy is inherited family with X - linked pattern in these cases, the associated gene is located on chromosome X. In women, a mutation in one of the two copies of the gene in every cell increases the risk of developing heart disease, but women with a mutation of this type can not develop the disease. In males, a mutation in the single gene copy in each cell causes the disease. A feature of the X - linked inheritance is that fathers can not pass X - linked traits to their sons chromosome.
Tests performed in IVAMI: in IVAMI perform the detection of mutations associated with dilated family cardiomyopathy, by complete PCR amplification of the exons of the genes TTN , ABCC9 , ACTC1 , ACTN2 , ANKRD1 , BAG3 , CRYAB , CSRP3 , DES , DMD , DSG2 , EYA4 , GATAD1 , LAMA4 , LDB3 , LMNA , MYBPC3 , MYH6 , MYH7 , MYPN , PLN , PSEN1 , PSEN2 , RBM20 , SCN5A , SGCD , TAZ , TCAP , TMPO , TNNC1 , TNNI3 , TNNT2 , TPM1 and VCL , respectively, and subsequent sequencing.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).