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D. K. Wheaton, R. K. Koenekoop, H. Khan, A. Takacs, D. R. Hoffman; Evaluation of Olfactory Function in Patients with X-linked Retinitis Pigmentosa (xlRP) Due to Mutations in the Retinitis Pigmentosa GTPase Regulator Gene (RPGR). Invest. Ophthalmol. Vis. Sci. 2009;50(13):1000.
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Mutations in the RPGR gene account for over 70% of xlRP. The encoded protein colocalizes with microtubles of the ciliary axoneme found in rod and cone photoreceptors and olfactory sensory neurons. RPGR together with CEP290 have been proposed to regulate entry of proteins including olfactory signal transduction intermediates into the cilium. In this investigation, we evaluate the potential for RPGR-induced dysfunction of olfaction in patients with retinal degeneration associated with xlRP.
Male patients (n=20) between 9 and 42 yrs of age were genotyped for RPGR mutations including the ORF15 hotspot. Genetic analysis was conducted by collaborating laboratories and screening services including eyeGENE. Olfactory function was assessed with the Smell Identification Test (Sensonics, Inc.). Forty odorant stimuli at suprathreshold levels were presented to each participant using 4 "scratch and sniff" booklets. Responses were scored and compared to published norms of the test kit.
The mean correct scores for xlRP patients was 34 out of 40 (range= 26-to-38) which places the cohort at the lower limit for normosmia (range= 34-to-40). Accounting for age and gender adjusted the cohort to the 31st percentile of normal olfactory function. Four patients were categorized as either mild or moderate microsmia. No difference was found between mean percentile scores in patients with ORF15 (n=9) vs non-ORF15 (n=11) mutations. Two odorants, cheddar cheese and motor oil, accounted for the most errors with 90% and 70% of study participants mis-identifying these stimuli. Detection of these odorants was significantly reduced compared to normal (p<0.001).
Since both RPGR and CEP290 are complexed near the ciliary basal body, it was anticipated that, like CEP290 (McEwen et al., PNAS, 2007), RPGR mutations would lead to deficits in the patient’s ability to smell. RPGR mutations in xlRP patients do result in ciliary dysfunction of photoreceptors leading to retinal degeneration, however RPGR mutations in the olfactory sensory neurons do not appear to markedly compromise this extraocular neurosensory function.
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