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Genetic study of pediatric hypertrophic cardiomyopathy in Egypt

Published online by Cambridge University Press:  05 October 2020

Rania K. Darwish ,
Alireza Haghighi ,
Zeinab S. Seliem ,
Sonia A. El-Saiedi ,
Nora H. Radwan ,
Dina F. El-Gayar ,
Nesrine S. Elfeel ,
Mohamed Abouelhoda  and
Dina A. Mehaney Open the ORCID record for Dina A. Mehaney [Opens in a new window]
Rania K. Darwish
Affiliation:
Clinical and Chemical Pathology Department, Faculty of Medicine, Cairo University, Cairo, Egypt Next-Generation sequencing Laboratory, Cairo University Children Hospital, Cairo, 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
Zeinab S. Seliem
Affiliation:
Pediatrics Department, Faculty of Medicine, Cairo University, Cairo, Egypt
Sonia A. El-Saiedi
Affiliation:
Pediatrics Department, Faculty of Medicine, Cairo University, Cairo, Egypt
Nora H. Radwan
Affiliation:
Clinical and Chemical Pathology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
Dina F. El-Gayar
Affiliation:
Clinical and Chemical Pathology Department, Faculty of Medicine, Cairo University, Cairo, 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
Dina A. Mehaney*
Affiliation:
Clinical and Chemical Pathology Department, Faculty of Medicine, Cairo University, Cairo, Egypt Next-Generation sequencing Laboratory, Cairo University Children Hospital, Cairo, Egypt
*
Author for correspondence: Dina Ahmed Mehaney, MD, Clinical and Chemical Pathology Department, Faculty of Medicine, Cairo University, Kasr Alainy St., Cairo 11562, Egypt. Tel: +20 1023123423; Fax: +20 23644383. E-mail: [email protected]
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Abstract

Paediatric cardiomyopathy is a progressive and often lethal disorder and the most common cause of heart failure in children. Despite their severe outcomes, their genetic etiology is still poorly characterised. The current study aimed at uncovering the genetic background of idiopathic primary hypertrophic cardiomyopathy in a cohort of Egyptian children using targeted next-generation sequencing. The study included 24 patients (15 males and 9 females) presented to the cardiomyopathy clinic of Cairo University Children’s Hospital with a median age of 2.75 (0.5–14) years. Consanguinity was positive in 62.5% of patients. A family history of hypertrophic cardiomyopathy was present in 20.8% of patients. Ten rare variants were detected in eight patients; two pathogenic variants (8.3%) in MBPC3 and MYH7, and eight variants of uncertain significance in MYBPC3, TTN, VCL, MYL2, CSRP3, and RBM20.

Here, we report on the first national study in Egypt that analysed sarcomeric and non-sarcomeric variants in a cohort of idiopathic paediatric hypertrophic cardiomyopathy patients using next-generation sequencing. The current pilot study suggests that paediatric hypertrophic cardiomyopathy in Egypt might have a particular genetic background, especially with the high burden of consanguinity. Including the genetic testing in the routine diagnostic service is important for a better understanding of the pathophysiology of the disease, proper patient management, and at-risk detection. Genome-wide tests (whole exome/genome sequencing) might be better than the targeted sequencing approach to test primary hypertrophic cardiomyopathy patients in addition to its ability for the identification of novel genetic causes.

Keywords

Paediatric hypertrophic cardiomyopathynext-generation sequencinggenetic diagnostics
Type
Original Article
Information
Cardiology in the Young , Volume 30 , Issue 12 , December 2020 , pp. 1910 - 1916
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Copyright
© The Author(s), 2020. Published by Cambridge University Press

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Footnotes

†

These authors contributed equally to this work.

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