Prioritization of Candidate Genes for Congenital Diaphragmatic Hernia in a Critical Region on Chromosome 4p16 using a Machine-Learning Algorithm

Danielle A. Callaway; Ian M. Campbell; Samantha R. Stover; Andres Hernandez-Garcia; Shalini N. Jhangiani; Jaya Punetha; Ingrid S. Paine; Jennifer E. Posey; Donna Muzny; Kevin P. Lally; James R. Lupski; Chad A. Shaw; Caraciolo J. Fernandes; Daryl A. Scott

doi:10.1055/s-0038-1655755

Journal of Pediatric Genetics, Table of Contents

J Pediatr Genet 2018; 07(04): 164-173
DOI: 10.1055/s-0038-1655755

Case Report

Georg Thieme Verlag KG Stuttgart · New York

Prioritization of Candidate Genes for Congenital Diaphragmatic Hernia in a Critical Region on Chromosome 4p16 using a Machine-Learning Algorithm

Danielle A. Callaway

¹Department of Pediatrics, Baylor College of Medicine, Houston, Texas, United States

,

Ian M. Campbell

²Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States

,

Samantha R. Stover

³Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States

,

Andres Hernandez-Garcia

³Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States

,

Shalini N. Jhangiani

³Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States

⁴Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, United States

,

Jaya Punetha

³Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States

,

Ingrid S. Paine

³Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States

,

Jennifer E. Posey

³Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States

,

Donna Muzny

³Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States

⁴Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, United States

,

Kevin P. Lally

⁵Department of Pediatric Surgery, McGovern Medical School at UT Health, Houston, Texas, United States

,

James R. Lupski

³Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States

⁴Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, United States

⁶Division of Neonatology, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, United States

,

Chad A. Shaw

³Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States

,

Caraciolo J. Fernandes

⁶Division of Neonatology, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, United States

,

Daryl A. Scott

³Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States

⁷Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas, United States

› Author Affiliations

Abstract

Wolf–Hirschhorn syndrome (WHS) is caused by partial deletion of the short arm of chromosome 4 and is characterized by dysmorphic facies, congenital heart defects, intellectual/developmental disability, and increased risk for congenital diaphragmatic hernia (CDH). In this report, we describe a stillborn girl with WHS and a large CDH. A literature review revealed 15 cases of WHS with CDH, which overlap a 2.3-Mb CDH critical region. We applied a machine-learning algorithm that integrates large-scale genomic knowledge to genes within the 4p16.3 CDH critical region and identified FGFRL1, CTBP1, NSD2, FGFR3, CPLX1, MAEA, CTBP1-AS2, and ZNF141 as genes whose haploinsufficiency may contribute to the development of CDH.

Keywords

Wolf–Hirschhorn syndrome - congenital diaphragmatic hernia - machine-learning algorithm

Full Text

References

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Supplementary Material