Sarcomere Mutations in Cardiomyopathy With Left Ventricular Hypertrabeculation

Department of Medicine, The University of Chicago, Chicago, Ill, USA.
Circulation Cardiovascular Genetics (Impact Factor: 4.6). 10/2009; 2(5):442-9. DOI: 10.1161/CIRCGENETICS.109.861955
Source: PubMed


Mutations in the genes encoding sarcomere proteins have been associated with both hypertrophic and dilated cardiomyopathy. Recently, mutations in myosin heavy chain (MYH7), cardiac actin (ACTC), and troponin T (TNNT2) were associated with left ventricular noncompaction, a form of cardiomyopathy characterized with hypertrabeculation that may also include reduced function of the left ventricle.
We used clinically available genetic testing on 3 cases referred for evaluation of left ventricular dysfunction and noncompaction of the left ventricle and found that all 3 individuals carried sarcomere mutations. The first patient presented with neonatal heart failure and was referred for left ventricular noncompaction cardiomyopathy. Genetic testing found 2 different mutations in MYBPC3 in trans. The first mutation, 3776delA, Q1259fs, rendered a frame shift at 1259 of cardiac myosin-binding protein C and the second mutation was L1200P. The frameshift mutation was also found in this mother who displayed mild echocardiographic features of cardiomyopathy, with only subtle increase in trabeculation and an absence of hypertrophy. A second pediatric patient presented with heart failure and was found to carry a de novo MYH7 R369Q mutation. The third case was an adult patient with dilated cardiomyopathy referred for ventricular hypertrabeculation. This patient had a family history of congestive heart failure, including pediatric onset cardiomyopathy where 3 individuals in the family were found to have the MYH7 mutation R1250W.
Genetic testing should be considered for cardiomyopathy with hypertrabeculation.

9 Reads
  • Source
    • "Up to 64% of isolated LVNC has been reported to be familial, mostly consistent with an autosomal dominant mode of inheritance [18]. Mutations in several genes coding for sarcomeric proteins have been described in LVNC, such as β-myosin heavy chain (MYH7), cardiac myosin-binding protein C (MYBPC3), α-cardiac actin (ACTC1), cardiac troponin T (TNNT2), α-tropomyosin (TPM1) and cardiac troponin I (TNNI3) [18–21]. MYH7 has been reported to be the most frequent disease gene in LVNC in the absence of CHD [18, 19]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Ebstein's anomaly is a rare congenital heart malformation characterised by adherence of the septal and posterior leaflets of the tricuspid valve to the underlying myocardium. Associated abnormalities of left ventricular morphology and function including left ventricular noncompaction (LVNC) have been observed. An association between Ebstein's anomaly with LVNC and mutations in the sarcomeric protein gene MYH7, encoding β-myosin heavy chain, has been shown by recent studies. This might represent a specific subtype of Ebstein's anomaly with a Mendelian inheritance pattern. In this review we discuss the association of MYH7 mutations with Ebstein's anomaly and LVNC and its implications for the clinical care for patients and their family members.
    Netherlands heart journal: monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation 05/2011; 21(3). DOI:10.1007/s12471-011-0141-1 · 1.84 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Summary form only given, as follows. We report on the design of a novel frequency-doubling millimeter-wave amplifier (MWA). The MWA is a very compact, lightweight, fixed-frequency source capable of producing several kilowatts of microwave radiation in a frequency range between 1-50 GHz with an efficiency >60% and 20-30 dB gain. The MWA makes use of very narrow electron bunches to efficiently produce microwaves in a TM output cavity at the output frequency ω. Bunching of a small diameter electron beam is produced in a deflection “chopper” cavity operating at the drive frequency ω/2. This mechanism does not require a focusing system. We present a MWA design, including 2-1/2D and 3D particle-in-cell simulations performed on MAGIC and SOS, respectively. MWA design, ~1 kW of 20 GHz radiation is obtained with an efficiency of ~70% and 20 dB gain. Potential applications of the MWA are airborne systems, satellite communications, wireless systems, and the Microwave Power Module
    IEEE International Conference on Plasma Science 01/1997; DOI:10.1109/PLASMA.1997.604925
  • [Show abstract] [Hide abstract]
    ABSTRACT: We present a system for online Chinese signature verification which is based on the voting result of nine verification experts. First, we briefly describe the individual verification experts. Then, a voting method for expert combination is discussed. Finally, the performance of the combination is demonstrated in several practical experiments which show a high success rate of verification
    Security Technology, 1997. Proceedings. The Institute of Electrical and Electronics Engineers 31st Annual 1997 International Carnahan Conference on; 11/1997
Show more