Elsevier

Ophthalmology

Volume 111, Issue 7, July 2004, Pages 1410-1414
Ophthalmology

Original article
Novel mutations in the arrestin gene and associated clinical features in Japanese patients with Oguchi's disease

https://doi.org/10.1016/j.ophtha.2003.11.006Get rights and content

Abstract

Purpose

Only 2 mutations in the arrestin gene have been previously reported to be associated with Oguchi's disease, a homozygous Asn309(1-bp del) mutation in Japanese families and a homozygous Arg193stop mutation in an Indian family. The aim of this article is to report 2 novel mutations in the arrestin gene in 2 Japanese patients with Oguchi's disease and to describe the clinical features with the mutations.

Design

Molecular genetic study and observational case report.

Participants

Two unrelated Japanese patients with Oguchi's disease associated with novel arrestin mutations.

Methods

Genomic DNA was extracted from leukocytes of the peripheral blood, and exons 2 through 16 of the arrestin gene were amplified by polymerase chain reaction and directly sequenced. A complete ophthalmologic examination was performed, including best-corrected visual acuity, slit-lamp and fundus examinations, fundus photography, and electroretinography (ERG).

Main outcome measures

Direct sequencing of the arrestin gene, evaluation of visual acuity, refraction, and ERG.

Results

Three arrestin gene mutations were identified in 2 patients. A compound heterozygous mutation, Arg175stop and Asn309(1-bp del), was identified in 1 patient with Oguchi's disease. The former mutation has not been reported, whereas the latter is known to be a frequent mutation in Oguchi's disease in Japanese families. In a second patient, another novel mutation was detected in the gene, a homozygous Arg292stop mutation. Both patients demonstrated characteristic features of Oguchi's disease, including night blindness, golden-yellow discoloration of the retina, absent rod ERG response, and “negative” type bright-flash ERG after 30 minutes of dark adaptation.

Conclusions

The existence of 2 novel mutations of the arrestin gene in 2 unrelated Japanese patients strongly supports the previous data that arrestin gene mutations are associated with Oguchi's disease. All of the mutations in the arrestin gene that have been identified in Oguchi's disease are null mutations, indicating that only critical gene defects in the arrestin gene are associated with Oguchi's disease.

Section snippets

Patients and methods

This study conformed to the tenets of the Declaration of Helsinki, and informed consent was obtained from the subjects after an explanation of the purpose of this study. Two unrelated Japanese patients with Oguchi's disease who lived in the Chubu area, the middle of Japan, were involved. Both individuals examined have been followed in the Department of Ophthalmology of Nagoya University, Japan. The ophthalmologic examination included best-corrected visual acuity, refraction, biomicroscopy,

Case reports

Case 1 was a 23-year-old man who was referred because of night blindness when he was 9 years old. His best-corrected visual acuity was 1.5 in each eye, with refractive errors of −4.25 −4.00 ×175° in the right eye and −7.00 −2.25 ×175° in the left eye. The Goldmann kinetic visual fields showed no abnormalities. His pedigree showed no other member with night blindness or retinal disease, and no consanguinity was reported in his family (Fig 1A).

Case 2 was a 30-year-old man when he was first seen

Discussion

Patients with Oguchi's disease are rare even in Japan where the disease was first discovered.1 The disease is becoming even more rare because of the decreased number of consanguineous marriages. Oguchi's disease is associated with either an arrestin or a rhodopsin kinase gene mutation,5, 6 and it is hypothesized that the defect in the translated protein prolongs the half-life of photoactivated rhodopsin. Extended rhodopsin half-life prolongs the phototransduction signal, resulting in prolonged

Acknowledgements

The authors thank Masakazu Nagase, MSc, for technical assistance with the analysis of the arrestin gene.

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    Manuscript no. 230340.

    Supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology, Tokyo, Japan (MN, grant no.: B14370556; YM, grant no.: A13307048), and the Ministry of Health, Labor, and Welfare, Tokyo, Japan.

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