Get access

Screening of human LPHN3 for variants with a potential impact on ADHD susceptibility

Authors

  • Sabina Domené,

    1. Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland
    Search for more papers by this author
    • Sabina Domené and Horia Stanescu contributed equally to this study.

  • Horia Stanescu,

    1. Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland
    Search for more papers by this author
    • Sabina Domené and Horia Stanescu contributed equally to this study.

  • Deeann Wallis,

    1. Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas
    Search for more papers by this author
  • Bradford Tinloy,

    1. Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland
    Search for more papers by this author
  • Daniel E. Pineda,

    1. Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland
    Search for more papers by this author
  • Robert Kleta,

    1. Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland
    Search for more papers by this author
  • Mauricio Arcos-Burgos,

    1. Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland
    Search for more papers by this author
  • Erich Roessler,

    1. Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland
    Search for more papers by this author
  • Maximilian Muenke

    Corresponding author
    1. Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland
    • Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, 35 Convent Drive—MSC 3717, Building 35, Room 1B-203, Bethesda, MD 20892-3717.
    Search for more papers by this author

  • How to Cite this Article: Domené S, Stanescu H, Wallis D, Tinloy B, Pineda DE, Kleta R, Arcos-Burgos M, Roessler E, Muenke M. 2011. Screening of human LPHN3 for variants with a potential impact on ADHD susceptibility. Am J Med Genet Part B 156:11–18.

Abstract

Attention deficit hyperactivity disorder (ADHD) is the most common behavioral disorder in childhood, and often has effects detectable into adulthood. Advances in genetic linkage and association analysis have begun to elucidate some of the genetic factors underlying this complex disorder. Recently, we identified LPHN3, a novel ADHD susceptibility gene harbored in 4q, and showed that a LPHN3 common haplotype confers susceptibility to ADHD and predicts effectiveness of stimulant medication. Here we present the mutational analysis of the entire coding region of LPHN3 in a cohort of 139 ADHD subjects and 52 controls from across the USA. We identified 21 variants, of which 14 have been reported and 7 are novel. These include 5 missense, 8 synonymous, and 8 intronic changes. Interestingly, neither susceptibility nor protective haplotype alleles are associated with obviously significant coding region changes, or canonical splice site alterations, suggesting that non-coding variations determining the quantity and/or quality of LPHN3 isoforms are the likely contributors to this common behavioral disorder. © 2010 Wiley-Liss, Inc.

Get access to the full text of this article

Ancillary