No previous reports regarding phenotypes associated with RPGR gene or RP2 gene have been shown in Japanese patients with XlRP. In fact, only 12 mutations in the RP2 gene have been reported, and 1 of these mutations was a missense mutation and the rest were nonsense mutations.56 Furthermore, the clinical features of XlRP associated with the mutation in the RP2 gene have not been reported. In this report, we first described the ocular findings with the Leu253Arg mutation in the RP2 gene in a Japanese patient with XlRP. This mutation within exon2 occurred outside the region homologous to a cofactor C, where most of the reported mutations have been found. Although the precise effect of the Leu253Arg change on the protein product is still unclear, we can assume that a positive charge of arginine residue instead of a hydrophobic leucine residue can impede, to some extent, physiological structure and function of the RP2 protein.
The ocular finding in the affected male showed a severe form of RP; he had an impairment of night vision and a deterioration of central vision within the first two decades of life. These findings are similar to those in patients who had mutations in the RPGR gene1011 and in the RP2 gene.5
Recently it was reported that mutations in the RPGR gene and the RP2 gene were found in approximately 20% and 18%, respectively, of the patients with XlRP.512 In our study, we found mutations in approximately 4% of Japanese patients with XlRP, which implies that RP2 mutations are less frequent in Japanese patients than in European and American patients. One explanation of the low frequency of the mutation in the RP2 gene may be an ethnic difference.
This novel Leu253Arg mutation, which we first detected in a Japanese patient with XlRP, supports the theory that mutation in the RP2 gene causes XlRP in Japanese patients. In the present study, we did not detect nonsense mutation in RP2 gene, we could not examine the difference between the clinical features caused by the missense mutation and those by the nonsense mutation. Therefore, additional families with XlRP must be studied for mutations to ascertain the phenotype–genotype correlation in the RP2 gene.
From a clinical point of view, further correlations between specific mutations and their phenotypes are needed to augment our understanding not only of the molecular mechanism of diseases but also of diagnostic and prognostic values.
Supported in part by a grant from the Research Committee on Chorioretinal Degenerations and Optic Atrophy, the Ministry of Health and Welfare of the Japanese Government (Dr. Tamai; Tokyo, Japan); and a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, and Culture of the Japanese Government (Dr. Tamai, A-2-10307041), Tokyo, Japan.
Corresponding author: Yuko Wada, Department of Ophthalmology, Tohoku University School of Medicine, 1-1, Seiryo-machi, Aoba-ku, Sendai 980-77, Japan. firstname.lastname@example.org