Pediatric Cardiology

, Volume 39, Issue 8, pp 1676–1680 | Cite as

Targeted Next-Generation Sequencing of 406 Genes Identified Genetic Defects Underlying Congenital Heart Disease in Down Syndrome Patients

  • Khalid M. Alharbi
  • Abdelhadi H. Al-Mazroea
  • Atiyeh M. Abdallah
  • Yousef Almohammadi
  • S. Justin Carlus
  • Sulman BasitEmail author
Original Article


Down syndrome (DS) is the most common autosomal chromosome anomaly. DS is frequently associated with congenital heart disease (CHD). Patients with DS have 40–60% chance of having CHD. It means that CHD in DS is not only due to trisomy 21 and there are some other genetic factors underlying CHD in DS children. In this study, a total of 240 DNA samples from patients were analyzed including 100 patients with CHD only, 110 patients having CHD along with DS and 30 patients with isolated DS. A cardiovascular gene panel consisting of probes for 406 genes was used to screen DNA samples of all 240 patients for mutation identification. All variants were annotated and common variants were obtained. Briefly, 28 common variants (variants common in two or more than two individuals) were obtained in a group of samples containing DNA from DS patients having CHD as well, 63 variants were found to be unique to DS group of samples and 73 variants have been identified in patients with CHD only. In order to identify genomic variations determining the risk for CHD in DS, only those variants present in DS-CHD group and absent in isolated CHD and/or isolated DS group were considered for further analysis. Variants specific to DS-CHD group were further evaluated based on expression and function data and pathogenicity of the variant of interest. We have implicated mutations in GATA3, KCNH2, ENG, FLNA, and GUSB genes as an underlying risk factor for CHD in DS patients.


Down syndrome Congenital heart disease Sequencing Gene Mutations 



This study was funded by King Abdul Aziz City for Science and Technology (Grant No. AT-34-369).

Compliance with Ethical Standards

Conflict of interest

All authors declare that they have no conflict of interest.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the Taibah University ethical research committee, ethical review board of Madinah Maternity and Children Hospital and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed Consent

Informed consents were obtained from all individual participants included in the study.

Supplementary material

246_2018_1951_MOESM1_ESM.docx (43 kb)
Supplementary material 1 (DOCX 42 KB)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Pediatrics Department, College of MedicineTaibah University AlmadinahMedinaKingdom of Saudi Arabia
  2. 2.West Midlands Regional Genetics LaboratoryBirmingham Women’s NHS Foundation TrustBirminghamUK
  3. 3.Security Forces Medical CentreMedinaKingdom of Saudi Arabia
  4. 4.Center for Genetics and Inherited Diseases, College of MedicineTaibah University AlmadinahMedinaKingdom of Saudi Arabia

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