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A. Iannaccone, D.K. Breuer, X.F. Wang, S.F. Kuo, E.M. Normando, D. Cosgrove, A. Baldi, C.C. Morton, A. Swaroop, M.M. Jablonski; Clinical and Immunohistochemical Evidence for an X-linked Retinitis Pigmentosa Syndrome with Recurrent Infections and Hearing Loss in Association with an RPGR Mutation . Invest. Ophthalmol. Vis. Sci. 2003;44(13):4871.
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Purpose: To report a family with X-linked recessive retinitis pigmentosa (XLRP) associated with the unique phenotype of relapsing otitis media (ROM), recurrent upper respiratory tract infections (RUTI), and hearing loss (HL). This is the second such family reported (see Zito, ARVO 2001, abs.#3447). Methods: Patients were examined clinically and functionally with automated (dark- and light-adapted) and kinetic perimetry, electroretinogram (ERG), and pure tonal audiometry (PTI). Human autoptic retinal, bronchial, sinus, and cochlear sections, and monkey and mouse cochlear sections were stained with anti-RPGR antibodies to determine the RPGR expression patterns in these tissues. Results: Molecular studies demonstrated also in this family a change in the RPGR gene. Affected males and carrier females shared a G173R RPGR missense mutation. In childhood, the peripheral retina of affected males had a finely punched-out appearance but no bone spicules. The functional phenotype was that of classical RP with a rod>cone pattern of dysfunction, with partial preservation of rod responses. Female carriers were either asymptomatic and disease-free to functional testing, or showed late-onset mild patchy RP with a cone>rod pattern of dysfunction. PTI showed mixed HL in the affected males with ROM and RUTI, and sensorineural HL in the grandmother since age 41, who also had suffered with ROM. By immunohistochemistry, we confirmed the expression of RPGR in human retinal photoreceptors, and we documented RPGR expression in the epithelial lining of human bronchi and sinuses, and in the human, monkey and mouse cochlea. Conclusions: Males born with the G173R RPGR mutation have early-onset sizable reduction in both rod and cone function, whereas carriers have a cone-predominant phenotype, thereby further confirming the important role of RPGR for cone photoreceptor function. Both males and females with the G173R RPGR mutation are predisposed to ROM, RUTI and HL. Our findings provide additional evidence in favor of a broader phenotypic range in association with RPGR mutations than previously suspected and suggest an important role for RPGR in extraocular tissues, specifically, in the respiratory tract and in the cochlea.
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