April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Dominant Mutations In RP1L1 Are Responsible For Occult Macular Dystrophy
Masakazu Akahori; Kazushige Tsunoda; Yozo Miyake; Shoji Tsuji; Tomoaki Usui; Makoto Nakamura; Hisao Ohde; Takeshi Itabashi; Takeshi Iwata
Author Affiliations & Notes
  • Masakazu Akahori
    Laboratory of Cellular & Molecular Biology,
    National Inst of Sensory Organs, Meguro-ku, Tokyo, Japan
  • Kazushige Tsunoda
    National Inst of Sensory Organs, Meguro-ku, Tokyo, Japan
  • Yozo Miyake
    National Inst of Sensory Organs, Meguro-ku, Tokyo, Japan
    Aichi Medical University, Aichi-gun, Aichi-ken, Japan
  • Shoji Tsuji
    Department of Neurology, Graduate School of Medicine, The University of Tokyo, Bukyo-ku, Tokyo, Japan
  • Tomoaki Usui
    Division of Ophthalmology and Visual Science, Graduate School of Medical and Dental Sciences, Niigata University, Asahimachidori, Niigata, Japan
  • Makoto Nakamura
    Ophthalmology, Nakamura Eye Clinic, Nagoya, Japan
  • Hisao Ohde
    Department of Ophthalmology, School of Medicine, Keio University, Shinjuku-ku, Tokyo, Japan
  • Takeshi Itabashi
    Laboratory of Cellular & Molecular Biology,
    National Inst of Sensory Organs, Meguro-ku, Tokyo, Japan
  • Takeshi Iwata
    Laboratory of Cellular & Molecular Biology,
    National Inst of Sensory Organs, Meguro-ku, Tokyo, Japan
  • Footnotes
    Commercial Relationships  Masakazu Akahori, None; Kazushige Tsunoda, None; Yozo Miyake, None; Shoji Tsuji, None; Tomoaki Usui, None; Makoto Nakamura, None; Hisao Ohde, None; Takeshi Itabashi, None; Takeshi Iwata, None
  • Footnotes
    Support  Ministry of Health, Labour and Welfare of Japan
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 5385. doi:
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      Masakazu Akahori, Kazushige Tsunoda, Yozo Miyake, Shoji Tsuji, Tomoaki Usui, Makoto Nakamura, Hisao Ohde, Takeshi Itabashi, Takeshi Iwata; Dominant Mutations In RP1L1 Are Responsible For Occult Macular Dystrophy. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5385.

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Abstract

Purpose: : Occult macular dystrophy (OMD) is an inherited macular dystrophy characterized by progressive loss of macular function but normal ophthalmoscopic appearance. Typical OMD is characterized by a central cone dysfunction leading to a loss of vision despite normal ophthalmoscopic appearance, normal fluorescein angiography, and normal full-field electroretinogram (ERGs), but the amplitudes of the focal macular ERGs and multifocal ERGs are significantly reduced at the central retina.

Methods: : Linkage analysis of two OMD families was performed by Affymetrix SNP 6.0 array and the SNP High Throughput Linkage analysis system (SNP HiTLink). Coding exons of four protein coding genes in the candidate region were analyzed for sequence variations by direct DNA-sequencing. Immuno-staining for RP1L1 was carried out on frozen sections of normal cynomolgus and paraffin section of normal marmoset.

Results: : Genome wide linkage analysis localized the disease locus to chromosome 8p22-p23. Among the 128 genes in the associated region, 22 genes were expressed in the retina, and four candidate genes were selected. No mutations were found in the first three candidate genes, methionine sulfoxide reductase A (MSRA), GATA binding 4 (GATA4), and pericentriolar material 1 (PCM1), however, amino acid substitution of p.Arg45Trp in retinitis pigmentosa 1-like 1 (RP1L1) was found in three OMD families and p.Trp960Arg in a remaining OMD family. These two mutations were detected in all affected individuals but none in 876 controls. Immunohistochemistry of RP1L1 in the retina section of cynomolgus and marmoset monkey revealed expression in the inner segment of rod and cone photoreceptor, supporting a role of RP1L1 in the photoreceptors that, when disrupted by mutation, leads to OMD.

Conclusions: : Identification of RP1L1 mutations as causative for OMD has potentially broader implications for understanding the differential cone photoreceptor functions in the fovea and the peripheral retina.

Keywords: linkage analysis • macula/fovea 
© 2011, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Permission to republish any abstract or part of an abstract in any form must be obtained in writing from the ARVO Office prior to publication.
Copyright © 2024 Association for Research in Vision and Ophthalmology.
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