Three novel mutations of the RPGR gene exon ORF15 in three Japanese families with X-linked retinitis pigmentosa

We describe three new mutations in a recently identified exon, ORF15, of th e retinitis pigmentosa GTPase regulator gene (RPGR) in three unrelated Japa nese families (Families 1-3) with X-linked retinitis pigmentosa (XLRP). The affected males had typical retinitis pigmentosa (RP), whereas the obligate carrier females showed a wide clinical spectrum, ranging from minor sympto ms to severe visual disability. Some carrier females in Families 1 and 2 sh owed typical RP, most carriers manifested high myopia and astigmatism, and their corrected visual acuity was insufficient. They showed an impairment o f cone function following the rod dysfunction and accompanied by refractive errors. Microsatellite analysis of Family 1 revealed that the RP in the fa mily was linked to the RP3 locus. Although one patient in the family had no mutation in the previously published exons 1-19 including exon 15a, he had a single-nucleotide insertion in exon ORF15 (g.ORF15 + 753-754 insG). Like wise, patients in Families 2 and 3 had two-base insertion/deletion in the e xon, i.e., g.ORF15 + 833-834delGG and g.ORF15 + 861-862insGG, respectively. These insertional/deletional mutations observed in the three families are all different and new, and are predicted to lead to a frameshift, resulting in a truncated protein. These findings may sup-port the previous hypothesi s that RPGR-ORF15 is a mutational hot spot. (C) 2001 Wiley-Liss, Inc.