A NOVEL HOMOZYGOUS ILE535ASN MUTATION IN THE ROD CGMP PHOSPHODIESTERASE BETA-SUBUNIT GENE IN 2 BROTHERS OF A JAPANESE FAMILY WITH AUTOSOMALRECESSIVE RETINITIS-PIGMENTOSA

Purpose. Recently, mutations in several genes have been identified as being responsible fnr the pathogenesis of autosomal recessive retiniti s pigmentosa (arRP). These genes include rhodopsin, beta-subunit of ro d cGMP phosphodiesterase (PDEB), alpha-subunit of rod cGMP phosphodies terase (PDEA), and alpha-subunit of rod cGMP-gated channel. We here at tempted to identify a novel mutation in the PDEB gene in Japanese arRP patients. Methods. Using the PCR-SSCP method, sequencing analysis, an d restriction endonuclease digestion assay, we analyzed the PDEB gene in 17 Japanese families with non-dominant retinitis pigmentosa. Result s. A novel Ile535Asn mutation was identified in two patients in a sing le 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 heter ozygous. Conclusions. Isoleucine at codon 535 in the PDEB gene is cons erved among various mammals. Missense mutations of the PDEB gene causi ng arRP have been reported in a limited region (codon 527-codon 699) i n which codon 535 is located. Thus, the Ile535Asn mutation is an addit ional missense mutation which is responsible for the pathogenesis of a r RP.