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Heterozygous deletion of the OPA1 gene in patients with dominant optic atrophy

  • Clinical Investigation
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Japanese Journal of Ophthalmology Aims and scope Submit manuscript

Abstract

Purpose

Several OPA1 variants cause dominant optic atrophy (DOA), the most common hereditary optic atrophy. Here, we describe a newly discovered OPA1 deletion in 3 patients with DOA.

Methods

A female proband, her brother, and her mother underwent complete ophthalmologic examinations that included optical coherence tomography and visual field assessments using a Humphrey Field Analyzer with both standard automated perimetry (SAP) and short-wavelength automated perimetry (SWAP). Genomic DNA from each patient was examined to detect genomic rearrangements involving OPA1; the genetic analysis involved both multiplex ligation probe amplification and conventional Sanger sequencing.

Results

Each patient had temporal optic disc pallor and significant thinning of the retinal nerve fiber layer in both eyes, although there was phenotypic variability among the patients that ranged from asymptomatic to moderately decreased visual acuity. For the affected brother and mother, the mean deviation values from SAP were within the normal range, whereas those from SWAP were significantly below the normal range (P < .05). The genetic analysis identified a newly discovered heterozygous deletion that encompasses exons 9–14 and revealed a breakpoint junction that directly connects intron 8 to intron 14.

Conclusions

This newly described deletion is likely to lead to loss of function in the functionally important GTPase domain encoded by exons 9–16, and the heterozygosity suggested that haploinsufficiency caused the phenotypes. The deletion may be associated with mild DOA phenotypes ranging from asymptomatic to moderately decreased visual acuity.

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Acknowledgements

This study was supported in part by JSPS Kakenhi Grants [Nos. 26462674 (KT) and 25462738 (TH)] and by the Japan Agency for Medical Research and Development, Practical Research Project for Rare/Intractable Diseases [No. 15ek0109072h0002 (TI)].

Author information

Authors and Affiliations

  1. Department of Ophthalmology, The Jikei University School of Medicine, Katsushika Medical Center, 6-41-2 Aoto, Katsushika-ku, Tokyo, 125-8506, Japan

    Takaaki Hayashi

  2. Department of Ophthalmology, The Jikei University School of Medicine, Tokyo, Japan

    Hiroyuki Sasano, Satoshi Katagiri & Hiroshi Tsuneoka

  3. Laboratory of Visual Physiology, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan

    Kazushige Tsunoda

  4. Department of Ophthalmology, Nippon Medical School Chiba Hokusoh Hospital, Chiba, Japan

    Shuhei Kameya

  5. Department of Ophthalmology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan

    Mitsuru Nakazawa

  6. Division of Molecular and Cellular Biology, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan

    Takeshi Iwata

Authors
  1. Takaaki Hayashi
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  2. Hiroyuki Sasano
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  3. Satoshi Katagiri
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  4. Kazushige Tsunoda
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  5. Shuhei Kameya
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  6. Mitsuru Nakazawa
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  7. Takeshi Iwata
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  8. Hiroshi Tsuneoka
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Corresponding author

Correspondence to Takaaki Hayashi.

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Conflicts of interest

T. Hayashi, None; H. Sasano, None; S. Katagiri, None; K. Tsunoda, None; S. Kameya, None; M. Nakazawa, None; T. Iwata, None; H. Tsuneoka, Grants (Abbott Medical Optics, Alcon, Daiichi Sankyo, Kowa, MSD, NIDEK, Otsuka, Santen, Senju), Lecture fees (Abbott Medical Optics, Alcon, Bausch & Lomb, HOYA, Kowa, NIDEK, Otsuka, Pfizer, Santen, Senju).

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Hayashi, T., Sasano, H., Katagiri, S. et al. Heterozygous deletion of the OPA1 gene in patients with dominant optic atrophy. Jpn J Ophthalmol 61, 395–401 (2017). https://doi.org/10.1007/s10384-017-0522-0

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  • DOI: https://doi.org/10.1007/s10384-017-0522-0

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