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De novo EEF1A2 mutations in patients with characteristic facial features, intellectual disability, autistic behaviors and epilepsy

Authors

  • J. Nakajima,

    1. Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan
    2. Department of Pediatrics, Tokyo Medical University, Shinjuku, Japan
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  • N. Okamoto,

    1. Department of Medical Genetics, Osaka Medical Center and Research Institute for Maternal and Child Health, Izumi, Japan
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  • J. Tohyama,

    1. Department of Pediatrics, Epilepsy Center, Nishi-Niigata Chuo National Hospital, Niigata, Japan
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  • M. Kato,

    1. Department of Pediatrics, Yamagata University Faculty of Medicine, Yamagata, Japan
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  • H. Arai,

    1. Department of Pediatric Neurology, Morinomiya Hospital, Osaka, Japan
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  • O. Funahashi,

    1. Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan
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  • Y. Tsurusaki,

    1. Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan
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  • M. Nakashima,

    1. Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan
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  • H. Kawashima,

    1. Department of Pediatrics, Tokyo Medical University, Shinjuku, Japan
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  • H. Saitsu,

    1. Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan
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  • N. Matsumoto,

    Corresponding author
    1. Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan
    • Corresponding authors: Noriko Miyake, MD, PhD, Department of Human Genetics, Yokohama City University Graduate School of Medicine, Fukuura 3-9, Kanazawa-ku, Yokohama 236-0004, Japan

      Tel.: +81 45 787 2606;

      fax: +81 45 786 5219;

      e-mail: nmiyake@yokohama-cu.ac.jp

      and

      Naomichi Matsumoto, MD, PhD

      e-mail: naomat@yokohama-cu.ac.jp

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  • N. Miyake

    Corresponding author
    1. Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan
    • Corresponding authors: Noriko Miyake, MD, PhD, Department of Human Genetics, Yokohama City University Graduate School of Medicine, Fukuura 3-9, Kanazawa-ku, Yokohama 236-0004, Japan

      Tel.: +81 45 787 2606;

      fax: +81 45 786 5219;

      e-mail: nmiyake@yokohama-cu.ac.jp

      and

      Naomichi Matsumoto, MD, PhD

      e-mail: naomat@yokohama-cu.ac.jp

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  • The authors declare that they have no conflicts of interest.

Abstract

Eukaryotic elongation factor 1, alpha-2 (eEF1A2) protein is involved in protein synthesis, suppression of apoptosis, and regulation of actin function and cytoskeletal structure. EEF1A2 gene is highly expressed in the central nervous system and Eef1a2 knockout mice show the neuronal degeneration. Until now, only one missense mutation (c.208G > A, p.Gly70Ser) in EEF1A2 has been reported in two independent patients with neurological disease. In this report, we described two patients with de novo mutations (c.754G > C, p.Asp252His and c.364G > A, p.Glu122Lys) in EEF1A2 found by whole-exome sequencing. Common clinical features are shared by all four individuals: severe intellectual disability, autistic behavior, absent speech, neonatal hypotonia, epilepsy and progressive microcephaly. Furthermore, the two patients share the similar characteristic facial features including a depressed nasal bridge, tented upper lip, everted lower lip and downturned corners of the mouth. These data strongly indicate that a new recognizable disorder is caused by EEF1A2 mutations.

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