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Dose dependent expression of HDAC4 causes variable expressivity in a novel inherited case of brachydactyly mental retardation syndrome

Authors

  • Benjamin Morris,

    1. Department of Human and Molecular Genetics, Virginia Commonwealth University School of Medicine, Richmond, Virginia
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  • Cécile Etoubleau,

    1. Département de Pédiatrie, Hôpital Universitaire de Limoges, Limoges Cedex, France
    2. Département d'Histologie et Cytogénétique, CHREC, Hôpital Universitaire de Limoges, Faculté de Médecine, Limoges Cedex, France
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  • Sylvie Bourthoumieu,

    1. Département d'Histologie et Cytogénétique, CHREC, Hôpital Universitaire de Limoges, Faculté de Médecine, Limoges Cedex, France
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  • Sandrine Reynaud-Perrine,

    1. Département d'Histologie et Cytogénétique, CHREC, Hôpital Universitaire de Limoges, Faculté de Médecine, Limoges Cedex, France
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  • Cécile Laroche,

    1. Département de Pédiatrie, Hôpital Universitaire de Limoges, Limoges Cedex, France
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  • Aziza Lebbar,

    1. Laboratoire de Cytogénétique. Groupe Hospitalier Cochin-Broca-Hotel Dieu, APHP.123 Bd de Port Royal. Paris, France
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  • Catherine Yardin,

    1. Département d'Histologie et Cytogénétique, CHREC, Hôpital Universitaire de Limoges, Faculté de Médecine, Limoges Cedex, France
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  • Sarah H. Elsea

    Corresponding author
    1. Department of Human and Molecular Genetics, Virginia Commonwealth University School of Medicine, Richmond, Virginia
    2. Department of Pediatrics, Virginia Commonwealth University School of Medicine, Richmond, Virginia
    • Departments of Pediatrics and Human and Molecular Genetics, Virginia Commonwealth University School of Medicine, Richmond, VA 23298.
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  • How to Cite this Article: Morris B, Etoubleau C, Bourthoumieu S, Reynaud-Perrine S, Laroche C, Lebbar A, Yardin C, Elsea SH. 2012. Dose dependent expression of HDAC4 causes variable expressivity in a novel inherited case of brachydactyly mental retardation syndrome. Am J Med Genet Part A. 158A:2015–2020.

  • Catherine Yardin and Sarah H. Elsea contributed equally to this work.

Abstract

Histone deacetylase 4 (HDAC4) serves important roles in multiple human systems, including neurological, cardiac, and skeletal functions. Mutation or deletion of HDAC4 causes brachydactyly mental retardation syndrome (BDMR), a disorder that includes intellectual disability, behavioral abnormalities, autism spectrum disorder, and craniofacial and skeletal anomalies, including brachydactyly type E. We present a case of familial BDMR, including a parent with mild symptoms of the disorder and a child exhibiting a more severe phenotype. Cytogenetic testing showed a cryptic balanced translocation in the mother that resulted in a 2q37.1 monosomy and a 10q26.1 trisomy in the son. Gene expression analyses demonstrated 67% HDAC4 expression in the mother and 23% HDAC4 expression in the son relative to normal controls, lending evidence to the hypothesis that HDAC4 modulates severity of this disorder in a dosage-dependent manner. © 2012 Wiley Periodicals, Inc.

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