July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
A novel homozygous in-frame deletion of GNAT1 gene cause golden discolouration of the fundus and reduced dark-adapted ERG similar to characteristics of Oguchi disease in a Japanese family
Author Affiliations & Notes
  • Shuhei Kameya
    Ophthaolmology, Nippon Medical School Chiba Hokusoh Hospital, Japan
  • Daiki Kubota
    Ophthaolmology, Nippon Medical School Chiba Hokusoh Hospital, Japan
  • Kiyoko Gocho
    Ophthaolmology, Nippon Medical School Chiba Hokusoh Hospital, Japan
  • Sachiko Kikuchi
    Ophthaolmology, Nippon Medical School Chiba Hokusoh Hospital, Japan
  • Kunihiko Yamaki
    Ophthaolmology, Nippon Medical School Chiba Hokusoh Hospital, Japan
  • Tsutomu Igarashi
    Ophthalmology, Nippon Medical School, Japan
  • Hiroshi Takahashi
    Ophthalmology, Nippon Medical School, Japan
  • Nobuo Ishida
    Ishida Eye Clinic, Japan
  • Kazutoshi Yoshitake
    Division of Molecular and Cellular Biology, National Institute of Sensory Organs, Japan
  • Takeshi Iwata
    Division of Molecular and Cellular Biology, National Institute of Sensory Organs, Japan
  • Atsushi Mizota
    Ophthalmology, Teikyo University, Japan
  • Footnotes
    Commercial Relationships   Shuhei Kameya, None; Daiki Kubota, None; Kiyoko Gocho, Spouse-Imagineyes (E); Sachiko Kikuchi, None; Kunihiko Yamaki, None; Tsutomu Igarashi, None; Hiroshi Takahashi, None; Nobuo Ishida, None; Kazutoshi Yoshitake, None; Takeshi Iwata, None; Atsushi Mizota, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 2927. doi:
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      Shuhei Kameya, Daiki Kubota, Kiyoko Gocho, Sachiko Kikuchi, Kunihiko Yamaki, Tsutomu Igarashi, Hiroshi Takahashi, Nobuo Ishida, Kazutoshi Yoshitake, Takeshi Iwata, Atsushi Mizota; A novel homozygous in-frame deletion of GNAT1 gene cause golden discolouration of the fundus and reduced dark-adapted ERG similar to characteristics of Oguchi disease in a Japanese family. Invest. Ophthalmol. Vis. Sci. 2019;60(9):2927.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : GNAT1, encoding the alpha-subunit of transducin in rod, is an important element of the phototransduction cascade. Defects in GNAT1 are very rare and have been identified in autosomal dominant and autosomal recessive congenital stationary night blindness (CSNB) and autosomal recessive rod-cone dystrophy with reduced rod ERG response in all patients reported. We performed observational clinical study to identify the phenotype-genotype relationship of a non-consanguineous Japanese family with GNAT1 mutation.

Methods : Detailed ophthalmic examinations including ISCEV standard ERG were performed on the patients and their family member. Whole exome sequencing (WES) was applied to the DNA obtained from the family member. Filtering with available genomic databases and in silico analyses were used to identify the disease causing variants. Sanger sequencing and co-segregation analysis of the family members were performed to identify the most likely pathogenic variant.

Results : Two female (13 and 11 years old) and a male (15 years old) patients from a family had night blindness from their childhood. Fundus appearance of these three patients showed a mild golden-yellow discoloration. Mizuo-Nakamura phenomenon had not been observed with three hours dark adaptation. Electrophysiological analysis revealed distinguished a-wave of rod responses and severely reduced a- and b-wave of mixed rod-cone responses with electronegative form in all patients. Cone responses are mildly reduced in two patients and severely reduced in a female patient. Dark adapted responses are similar to that of Oguchi disease in these patients. Using WES on the DNA sample of the family, we identified a homozygous 1 amino-acid in-frame deletion c.818_820delAGA, p.Lys273del in the GNAT1. Variants were verified by Sanger sequencing and were co-segregated with the disease in five members of the family. Parents were not consanguineous, however both parents harbor same heterozygous mutation. According to ACMG standards and guideline, the variant was classified into pathogenic.

Conclusions : Our data indicate that the mutation of GNAT1 can cause CSNB with golden discolouration of the fundus and reduced dark-adapted ERG similar to characteristics of Oguchi disease.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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