A novel homozygous Ile535Asn mutation in the rod cGMP phosphodiesterase β-subunit gene in two brothers of a Japanese family with autosomal recessive retinitis pigmentosa

Purpose. Recently, mutations in several genes have been identified as being responsible for the pathogenesis of autosomal recessive retinitis pigmentosa (arRP). These genes include rhodopsin, β-subunit of rod cGMP phosphodiesterase (PDEB), α-subunit of rod cGMP phosphodiesterase (PDEA), and α-subunit of rod cGMP-gated channel. We here attempted to identify a novel mutation in the PDEB gene in Japanese arRP patients. Methods. Using the PCR-SSCP method, sequencing analysis, and restriction endonuclease digestion assay, we analyzed the PDEB gene in 17 Japanese families with non-dominant retinitis pigmentosa. Results. A novel Ile535Asn mutation was identified in two patients in a single family and the mutation cosegregated with RP in this family. Among 90 unrelated healthy individuals, no one was identified as homozygous for this mutation, except for one individual who was found to be heterozygous. Conclusions. Isoleucine at codon 535 in the PDEB gene is conserved among various mammals. Missense mutations of the PDEB gene causing arRP have been reported in a limited region (codon 527-codon 699) in which codon 535 is located. Thus, the Ile535Asn mutation is an additional missense mutation which is responsible for the pathogenesis of arRP.