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S. Grover, G.A. Fishman, E.M. Stone; Clinical Features of a Severe Form of Autosomal Dominant Retinitis Pigmentosa in a Large Family with a Novel IMPDH1 Mutation (ARG231PRO) . Invest. Ophthalmol. Vis. Sci. 2003;44(13):540.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To describe the clinical features of a large family with a severe form of autosomal dominant retinitis pigmentosa (adRP) and a novel mutation (Arg231Pro) in the inosine-5’-monophosphate dehydrogenase, type 1 (IMPDH1) gene on chromosome 7q. Methods: Sixteen affected members in three generations from this family were examined. Visual acuity and ophthalmological examination findings were recorded on each patient. Goldmann visual fields were obtained in eight and electroretinograms (ERG’s) performed on three patients. Blood was obtained for DNA testing from 17 affected and two unaffected members of the family. Results: The ages of the patients ranged from four to 81 years at their most recent visit. All had an onset of nyctalopia in the first decade of life. Ten out of 16 (62.5%) patients had a visual acuity of hand motion or worse in both eyes. Seven out of these ten patients were in the age range of 29 to 40 years. Irrespective of age, the hallmark clinical features were "waxy"-appearing optic disc pallor, severely attenuated retinal vessels and diffuse midperipheral retinal pigment atrophy and clumping. Ten patients showed an atrophic-appearing macular lesion in both eyes. Nystagmus was present in six, optic nerve disc drusen in three and keratoconus in two patients. One patient had intraretinal and vitreous hemorrhage in each eye, associated with peripheral retinal neovascularization. In all eight patients on whom Goldmann visual fields could be performed, a severe restriction of visual fields to less than 10 degrees with a target V4e was observed. Consequently, an electroretinogram (ERG) measurement was performed on only three patients and the responses were nondetectable. Genetic testing identified a novel Arg231Pro mutation in the IMPDH1 gene on chromosome 7q in all 17 affected members and was negative in the two unaffected members of the family who were tested. Conclusions: A family with adRP and a novel mutation in the IMPDH1 gene showed a severe form of the disease with an early onset of visual symptoms, diffuse retinal pigmentary changes, markedly impaired visual acuity, severely restricted visual fields and nondetectable ERG’s. A severe clinical phenotype may be a hallmark of mutations in the IMPDH1 gene.
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