Pediatric Cardiology

, Volume 33, Issue 5, pp 757–763 | Cite as

Submicroscopic Chromosomal Copy Number Variations Identified in Children With Hypoplastic Left Heart Syndrome

  • Ashleigh R. Payne
  • Sheng-Wei Chang
  • Sara N. Koenig
  • Andrew R. Zinn
  • Vidu GargEmail author
Original Article


Hypoplastic left heart syndrome (HLHS), one of the most severe types of congenital heart disease (CHD), results in significant morbidity and mortality despite surgical palliation. The etiology of HLHS is unknown, but evidence supports genetic contributors. The authors hypothesized that submicroscopic chromosomal abnormalities exist in individuals with HLHS and are more frequent in those with additional birth defects. This study sought to determine the incidence and genomic location of submicroscopic chromosomal abnormalities in HLHS and potentially to identify novel genetic loci that may contribute to the disease. For this study, 43 children with HLHS were recruited and screened together with a control population of 16 subjects using array comparative genomic hybridization, also called chromosomal microarray, for chromosomal copy number variations (CNVs). A statistically greater number of CNVs were found in the HLHS group than in the control group (p < 0.03). The CNVs were predominantly small autosomal deletions and duplications (≤60,000 bp). The frequency of unique CNVs, those not previously reported in public databases, did not differ statistically between the HLHS subjects and the control subjects. No difference in the frequency of CNVs was noted between the patients with HLHS and additional anomalies and those with isolated HLHS. The identified CNVs did not harbor potential candidate genes for HLHS, but one microdeletion was located on chromosome 14q23, a genetic locus linked to left-sided CHD. The study data demonstrate that CNVs, specifically those relatively small in size, are more common in subjects with HLHS, but the frequency of large potentially disease-causing CNVs (>480,000 bp) did not differ between the HLHS and control populations.


Array comparative genome hybridization Congenital heart defects Developmental delay Genetics Hypoplastic left heart syndrome 



The authors thank the participating subjects and the Divisions of Cardiology and Cardiothoracic Surgery at Children’s Medical Center Dallas for assistance with clinical information, and Dr. K. L. McBride for critical review of the manuscript. This work was supported by a grant to Vidu Garg from the Children’s Heart Foundation.

Supplementary material

246_2012_208_MOESM1_ESM.docx (47 kb)
Supplementary material 1 (DOCX 46 kb)


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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Ashleigh R. Payne
    • 1
  • Sheng-Wei Chang
    • 4
  • Sara N. Koenig
    • 4
  • Andrew R. Zinn
    • 2
    • 3
  • Vidu Garg
    • 4
    Email author
  1. 1.Department of PediatricsUniversity of Texas Southwestern Medical CenterDallasUSA
  2. 2.Department of Internal MedicineUniversity of Texas Southwestern Medical CenterDallasUSA
  3. 3.McDermott Center for Human Growth and DevelopmentUniversity of Texas Southwestern Medical CenterDallasUSA
  4. 4.Center for Cardiovascular and Pulmonary Research and The Heart Center, Nationwide Children’s Hospital and Department of PediatricsThe Ohio State UniversityColumbusUSA

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