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


METHODS
Molecular genetic study and observational case report.


METHODS
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).


METHODS
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.
Nakamura
Makoto
M
Department of Ophthalmology, Nagoya University Graduate School of Medicine, Nagoya, Japan. makonaka@med.nagoya-u.ac.jp
Yamamoto
Shuji
S
Okada
Masaki
M
Ito
Sei
S
Tano
Yasuo
Y
Miyake
Yozo
Y
D000328:Adult; D019393:Arrestin / Q000235:genetics*; D004252:DNA Mutational Analysis; D004596:Electroretinography; D005091:Exons / Q000235:genetics; D005784:Gene Amplification; D006801:Humans; D007564:Japan; D008297:Male; D009154:Mutation; D009755:Night Blindness / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012029:Refraction, Ocular; D012160:Retina / Q000503:physiopathology; D014792:Visual Acuity
D019393:Arrestin