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Molecular analysis of dilated and left ventricular noncompaction cardiomyopathies in Egyptian children

Published online by Cambridge University Press:  26 May 2021

Dina A. Mehaney Open the ORCID record for Dina A. Mehaney [Opens in a new window] ,
Alireza Haghighi ,
Amira K. Embaby Open the ORCID record for Amira K. Embaby [Opens in a new window] ,
Reham A. Zeyada ,
Rania K. Darwish ,
Nesrine S. Elfeel ,
Mohamed Abouelhoda ,
Sonia A. El-Saiedi ,
Nadida A. Gohar  and
Zeinab S. Seliem
Dina A. Mehaney*
Affiliation:
Clinical and Chemical Pathology Department, Faculty of Medicine, Cairo University, Cairo, Egypt Next Generation Sequencing Laboratory, Cairo University Children Hospital, Egypt
Alireza Haghighi
Affiliation:
Division of Genetics, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA Department of Genetics, Harvard Medical School, Boston, MA, USA Howard Hughes Medical Institute, Brigham and Women’s Hospital, Boston, MA, USA
Amira K. Embaby
Affiliation:
Clinical and Chemical Pathology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
Reham A. Zeyada
Affiliation:
Clinical and Chemical Pathology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
Rania K. Darwish
Affiliation:
Clinical and Chemical Pathology Department, Faculty of Medicine, Cairo University, Cairo, Egypt Next Generation Sequencing Laboratory, Cairo University Children Hospital, Egypt
Nesrine S. Elfeel
Affiliation:
Pediatrics Department, Faculty of Medicine, Cairo University, Cairo, Egypt
Mohamed Abouelhoda
Affiliation:
Systems and Biomedical Engineering Department, Faculty of Engineering, Cairo University, Cairo, Egypt
Sonia A. El-Saiedi
Affiliation:
Pediatrics Department, Faculty of Medicine, Cairo University, Cairo, Egypt
Nadida A. Gohar
Affiliation:
Clinical and Chemical Pathology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
Zeinab S. Seliem
Affiliation:
Pediatrics Department, Faculty of Medicine, Cairo University, Cairo, Egypt
*
Author for correspondence: Dr D. A. Mehaney, MD, Clinical and Chemical Pathology Department, Faculty of Medicine, Cairo University, Kasr Alainy St., Cairo, 11562, Egypt. Tel: +201023123423; Fax: +2023644383. E-mail: [email protected]
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Abstract

Background:

Paediatric cardiomyopathy is a progressive, often lethal disorder and the most common cause of heart failure in children. Despite its severe outcomes, the genetic aetiology is still poorly characterised. High-throughput sequencing offers a great opportunity for a better understanding of the genetic causes of cardiomyopathy.

Aim:

The current study aimed to elucidate the genetic background of cardiomyopathy in Egyptian children.

Methods:

This hospital-based study involved 68 patients; 58 idiopathic primary dilated cardiomyopathy and 10 left ventricular noncompaction cardiomyopathy. Cardiomyopathy-associated genes were investigated using targeted next-generation sequencing.

Results:

Consanguinity was positive in 53 and 70% of dilated cardiomyopathy and left ventricular noncompaction cardiomyopathy patients, respectively. Positive family history of cardiomyopathy was present in 28% of dilated cardiomyopathy and 10% of the left ventricular noncompaction cardiomyopathy patients. In 25 patients, 29 rare variants were detected; 2 likely pathogenic variants in TNNI3 and TTN and 27 variants of uncertain significance explaining 2.9% of patients.

Conclusions:

The low genetic detection rate suggests that novel genes or variants might underlie paediatric cardiomyopathy in Egypt, especially with the high burden of consanguinity. Being the first national and regional report, our study could be a reference for future genetic testing in Egyptian cardiomyopathy children. Genome-wide tests (whole exome/genome sequencing) might be more suitable than the targeted sequencing to investigate the primary cardiomyopathy patients. Molecular characterisation of cardiomyopathies in different ethnicities will allow for global comparative studies that could result in understanding the pathophysiology and heterogeneity of cardiomyopathies.

Keywords

Dilated cardiomyopathyleft ventricular noncompaction cardiomyopathynext-generation sequencingpaediatricsEgypt
Type
Original Article
Information
Cardiology in the Young , Volume 32 , Issue 2 , February 2022 , pp. 295 - 300
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Copyright
© The Author(s), 2021. Published by Cambridge University Press

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Footnotes

*

Dina A. Mehaney, Alireza Haghighi, Rania K. Darwish, and Mohamed Abouelhoda are first authors on this review with a shared first co-authorship.

**

Sonia A. El-Saiedi, Nadida A. Gohar, and Zeinab S. Seliem Elhoda are the last authors on this review with a shared last co-authorship.

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