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M. Mura, C. Sereda, I.M. MacDonald, A. Iannaccone; Clinical and Functional Findings in a Family With Choroideremia Due to a Deletion of the Entire CHM Gene . Invest. Ophthalmol. Vis. Sci. 2005;46(13):534.
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Purpose: To report the clinical and functional characteristics of a family with choroideremia (CHM). Methods: Serial visual acuity (VA) assessments, fundus exams and dark– (DA) and light–adapted (LA) flash ERGs under anesthesia were performed over a range of flash intensities. LA (600nm) and DA (500 and 650nm) thresholds were also measured across the visual field. Records and history were reviewed for 5 males (65–75 yo) with advanced disease. Blood samples for molecular testing were obtained from the proband and his mother. Results: At age 4, the proband had a hypopigmented fundus with RPE mottling and punctate pigmentary deposits, but minimal atrophy. Rod–driven ERGs were reduced to 10% of the lowest normal limit. Responses over a range of flash intensities showed loss of scotopic sensitivity. Mixed DA rod–cone a– and b–waves were reduced to about 45 and 60% of the lowest normal limit to 0.32 log cd.s/m2 and to 50 and 80% to 1.0 log cd.s/m2 stimuli, respectively. LA cone–driven responses were near normal in size, but delayed in timing. Molecular studies showed a deletion of the entire CHM gene, including a 57–kb region upstream of exon 1. During the F/U period, his VA remained unchanged, but progressive night vision problems developed. Widespread coalescent areas of severe nummular atrophy of the RPE and choriocapillaris developed by age 6, sparing only the centermost macular region. ERGs showed a progressive decline in DA amplitudes and scotopic sensitivity, and development of overt cone loss. However, ERGs were larger than predictable from the fundus appearance. The ERG responses, 600nm, and 500nm thresholds of the 38–yo mother of the proband, who had retinal changes typical for a CHM carrier and night vision problems, were unexpectedly normal, while 650nm DA thresholds were elevated (∼ 1.0 and 1.5– 2.0 log units at macular and extramacular loci, respectively). The five affected males were reportedly legally blind, unable to drive since their 40s, but with fair central and peripheral vision between their 20s and 40s. Conclusions: Absence of the entire CHM gene causes severe CHM. Serial parallel ERGs and fundus exams in our proband documented rapid progression of rod disease early on, followed by cone disease. The deterioration in fundus appearance was even more strikingly rapid and exceeded the severity of the ERG losses. To our knowledge, this is the first instance of longitudinal documentation of the clinical and ERG phenotype in a child with molecularly characterized CHM and the first report of impaired DA cone–driven function in a carrier.
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