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

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Abstract

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.

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Acknowledgments

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.

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Authors and Affiliations

  1. Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA

    Ashleigh R. Payne

  2. Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA

    Andrew R. Zinn

  3. McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA

    Andrew R. Zinn

  4. Center for Cardiovascular and Pulmonary Research and The Heart Center, Nationwide Children’s Hospital and Department of Pediatrics, The Ohio State University, 700 Children’s Drive Room W302, Columbus, OH, 43205, USA

    Sheng-Wei Chang, Sara N. Koenig & Vidu Garg

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  1. Ashleigh R. Payne
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  5. Vidu Garg
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Correspondence to Vidu Garg.

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Payne, A.R., Chang, SW., Koenig, S.N. et al. Submicroscopic Chromosomal Copy Number Variations Identified in Children With Hypoplastic Left Heart Syndrome. Pediatr Cardiol 33, 757–763 (2012). https://doi.org/10.1007/s00246-012-0208-9

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  • DOI: https://doi.org/10.1007/s00246-012-0208-9

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