Congenital diaphragmatic hernia interval on chromosome 8p23.1 characterized by genetics and protein interaction networks

Publication: Research - peer-reviewJournal article – Annual report year: 2012

  • Author: Longoni, Mauro

    Massachusetts General Hospital, United States

  • Author: Hansen, Kasper Lage

    Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark

  • Author: Russell, Meaghan K.

    Massachusetts General Hospital, United States

  • Author: Loscertales, Maria

    Massachusetts General Hospital, United States

  • Author: Abdul‐Rahman, Omar A.

    University of Mississippi, United States

  • Author: Baynam, Gareth

    King Edward Memorial Hospital

  • Author: Bleyl, Steven B.

    University of Utah, United States

  • Author: Brady, Paul D.

    University Hospital Leuven, Belgium

  • Author: Breckpot, Jeroen

    University Hospital Leuven, Belgium

  • Author: Chen, Chih P.

    Mackay Memorial Hospital, Taiwan, Province of China

  • Author: Devriendt, Koenraad

    University Hospital Leuven, Belgium

  • Author: Gillessen‐Kaesbach, Gabriele

    Universität zu Lübeck, Germany

  • Author: Grix, Arthur W.

    Kaiser Permanente, United States

  • Author: Rope, Alan F.

    University of Utah, United States

  • Author: Shimokawa, Osamu

    Mitsubishi Chemical Medience Corporation, Japan

  • Author: Strauss, Bernarda

    Mercy Children's Hospital, Kansas City, United States

  • Author: Wieczorek, Dagmar

    Universitätsklinikum Essen, Germany

  • Author: Zackai, Elaine H.

    The Children's Hospital of Philadelphia, United States

  • Author: Coletti, Caroline M.

    Massachusetts General Hospital, United States

  • Author: Maalouf, Faouzi I.

    Massachusetts General Hospital, United States

  • Author: Noonan, Kristin M.

    Massachusetts General Hospital, United States

  • Author: Park, Ji H.

    Harvard Medical School, United States

  • Author: Tracy, Adam A.

    Massachusetts General Hospital

  • Author: Lee, Charles

    Harvard Medical School

  • Author: Donahoe, Patricia K.

    Massachusetts General Hospital, United States

  • Author: Pober, Barbara R.

    Massachusetts General Hospital, United States

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Chromosome 8p23.1 is a common hotspot associated with major congenital malformations, including congenital diaphragmatic hernia (CDH) and cardiac defects. We present findings from high‐resolution arrays in patients who carry a loss (n = 18) or a gain (n = 1) of sub‐band 8p23.1. We confirm a region involved in both diaphragmatic and heart malformations. Results from a novel CNVConnect algorithm, prioritizing protein–protein interactions between products of genes in the 8p23.1 hotspot and products of previously known CDH causing genes, implicated GATA4, NEIL2, and SOX7 in diaphragmatic defects. Sequence analysis of these genes in 226 chromosomally normal CDH patients, as well as in a small number of deletion 8p23.1 patients, showed rare unreported variants in the coding region; these may be contributing to the diaphragmatic phenotype. We also demonstrated that two of these three genes were expressed in the E11.5–12.5 primordial mouse diaphragm, the developmental stage at which CDH is thought to occur. This combination of bioinformatics and expression studies can be applied to other chromosomal hotspots, as well as private microdeletions or microduplications, to identify causative genes and their interaction networks. © 2012 Wiley Periodicals, Inc.
Original languageEnglish
JournalAmerican Journal of Medical Genetics. Part A
Volume158A
Issue number12
Pages (from-to)3148-3158
ISSN1552-4825
DOIs
StatePublished - 2012
Peer-reviewedYes
CitationsWeb of Science® Times Cited: 8
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