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Open Access 01-12-2016 | Research article

Mutation of a common amino acid in NKX2.5 results in dilated cardiomyopathy in two large families

Authors: Alan Hanley, Katie A. Walsh, Caroline Joyce, Michael A. McLellan, Sebastian Clauss, Amaya Hagen, Marisa A. Shea, Nathan R. Tucker, Honghuang Lin, Gerard J. Fahy, Patrick T. Ellinor

Published in: BMC Medical Genetics | Issue 1/2016

Abstract

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.

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Title: Mutation of a common amino acid in NKX2.5 results in dilated cardiomyopathy in two large families
Authors: Alan Hanley
Katie A. Walsh
Caroline Joyce
Michael A. McLellan
Sebastian Clauss
Amaya Hagen
Marisa A. Shea
Nathan R. Tucker
Honghuang Lin
Gerard J. Fahy
Patrick T. Ellinor
Publication date: 01-12-2016
Publisher: BioMed Central
Published in: BMC Medical Genetics / Issue 1/2016
Electronic ISSN: 1471-2350
DOI: https://doi.org/10.1186/s12881-016-0347-6

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Mutation of a common amino acid in NKX2.5 results in dilated cardiomyopathy in two large families

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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