[HTML][HTML] Mutation of a common amino acid in NKX2. 5 results in dilated cardiomyopathy in two large families
A Hanley, KA Walsh, C Joyce, MA McLellan… - BMC medical …, 2016 - Springer
BMC medical genetics, 2016•Springer
Background The genetic basis for dilated cardiomyopathy (DCM) can be difficult to
determine, particularly in familial cases with complex phenotypes. Next generation
sequencing may be useful in the management of such cases. Methods We report two large
families with pleiotropic inherited cardiomyopathy. In addition to DCM, the phenotypes
included atrial and ventricular septal defects, cardiac arrhythmia and sudden death.
Probands underwent whole exome sequencing to identify potentially causative variants …
determine, particularly in familial cases with complex phenotypes. Next generation
sequencing may be useful in the management of such cases. Methods We report two large
families with pleiotropic inherited cardiomyopathy. In addition to DCM, the phenotypes
included atrial and ventricular septal defects, cardiac arrhythmia and sudden death.
Probands underwent whole exome sequencing to identify potentially causative variants …
Background
The genetic basis for dilated cardiomyopathy (DCM) can be difficult to determine, particularly in familial cases with complex phenotypes. Next generation sequencing may be useful in the management of such cases.
Methods
We report two large families with pleiotropic inherited cardiomyopathy. In addition to DCM, the phenotypes included atrial and ventricular septal defects, cardiac arrhythmia and sudden death. Probands underwent whole exome sequencing to identify potentially causative variants.
Results
Each whole exome sequence yielded over 18,000 variants. We identified distinct mutations affecting a common amino acid in NKX2.5. Segregation analysis of the families support the pathogenic role of these variants.
Conclusion
Our study emphasizes the utility of next generation sequencing in identifying causative mutations in complex inherited cardiac disease. We also report a novel pathogenic NKX2.5 mutation.
Springer