This report describes dilated cardiomyopathy 2A, which is one of several forms of heart disease associated with the human cardiac troponin gene, TNNI3 (see MIM:191044). Information about fly models for this and related diseases can be found in the report 'cardiomyopathy, TNNI3-related' (FBhh0000420).
[updated Oct. 2016 by FlyBase; FBrf0222196]
Nonsyndromic isolated dilated cardiomyopathy (DCM) is characterized by left ventricular enlargement and systolic dysfunction, a reduction in the myocardial force of contraction. DCM usually presents with any one of the following: (1) Heart failure with symptoms of congestion (edema, orthopnea, paroxysmal nocturnal dyspnea) and/or reduced cardiac output (fatigue, dyspnea on exertion); (2) arrhythmias and/or conduction system disease; (3) thromboembolic disease (from left ventricular mural thrombus) including stroke. [from Dilated Cardiomyopathy Overview, pubmed:20301486 2016.01.26]
Dilated cardiomyopathy (CMD) is characterized by cardiac dilatation and reduced systolic function. CMD is the most frequent form of cardiomyopathy and accounts for more than half of all cardiac transplantations performed in patients between 1 and 10 years of age. A heritable pattern is present in 20 to 30% of cases. Most familial CMD pedigrees show an autosomal dominant pattern of inheritance, usually presenting in the second or third decade of life (summary by Levitas et al., 2010, pubmed:20551992). [from MIM:115200, 2016.01.27]
[CARDIOMYOPATHY, DILATED, 2A; CMD2A](https://omim.org/entry/611880)
[TROPONIN I, CARDIAC; TNNI3](https://omim.org/entry/191044)
Murphy et al. (2004, pubmed:15070570) studied a family in which the proband presented at 27 years of age with a history of progressive cardiac failure. Echocardiography showed a dilated left ventricle with poor function and he underwent cardiac transplantation at age 28, at which time his left ventricle end-diastolic volume (LVEDV) was 7.1 cm and fractional shortening was 4%. Histologic examination of the explanted heart showed myofibrillar loss, hyperchromatic nuclei, and myocyte hypertrophy, but no myofibril or myocyte disarray. His sister presented with heart failure at 29 years of age, with an LVEDV of 5.1 cm and fractional shortening of 19%. His parents and another sib were healthy, with normal electrocardiograms and echocardiograms. No family member showed evidence of cardiac conduction disease or skeletal myopathy. [From MIM:611880, 2016.02.02]
Dilated cardiomyopathy-2A (CMD2A) is caused by homozygous mutation in the gene encoding cardiac troponin I (TNNI3). [From MIM:611878, 2016.02.02]
The troponin complex is located on the thin filament of striated muscle and is composed of 3 component polypeptides: troponin I (TNNI1, MIM:191042; TNNI2, MIM:191043; and TNNI3, OMIM), troponin T (TNNT1, MIM:191041; and TNNT2, MIM:191045), and troponin C (TNNC1, MIM:191040; and TNNC2 MIM:191039). Three troponin T genes have been described on the basis of molecular cloning in humans and other vertebrates. These are expressed in a tissue-specific manner and encode the troponin T isoforms expressed in cardiac muscle, slow skeletal muscle (TNNT1), and fast skeletal muscle (TNNT3; MIM:600692). Each of these genes is subject to alternative splicing, resulting in the production of multiple tissue-specific isoforms. [From MIM:191044 and MIM:191045, 2016.02.02]
Many to one: 3 human to 1 Drosophila.
