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Z Yang, L Chorich, E Bond, S Thirumalaichary, H Zhang, E Plotkin, D Hunt, K Zhang; North Carolina Macular Dystrophy: Clinical Spectrum and Exclusion of Candidate Genes . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2826.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose:North Carolina macular dystrophy is an autosomal dominant, highly penetrant disease with congenital or infantile onset. It is generally non-progressive and shows a wide range of intrafamilial and interfamilial variations in clinical phenotypes. These clinical manifestations can be divided into three catageries. Grade 1 represents drusen in the central macula. Grade 2 denotes subretinal lesions or choroidal neovascularization. Grade 3 exhibits well demarcated chorioretinal atrophy with hyperpigmentation on the edge of the lesion. The disease gene (MCDR1) was assigned to 6q16 between D6S275 and D6S475. We report characterization of a previously undescribed family with MCDR1 and mutational screening of a novel candidate gene. Methods:Ophthalmoscopic examination, fundus photography, and fluorescein angiography were performed to identify individuals with North Carolina macular dystrophy. Genomic DNA was obtained from the blood of family members (6 affected, 6 unaffected) and was genotyped using polymorphic DNA markers encompassing MCDR1 locus. Each of six exons of a novel G-protein coupled receptor gene was amplified using PCR techniques and subjected to sequencing analysis. Results:Clinical examination of a Caucasian family revealed visual acuity ranging from 20/25 to 20/200. The clinical phenotypes were characterized by bilateral grade 1 lesions in 2 patients, grade 2 lesions in one patient, and grade 3 lesions in 3 patients. Linkage analysis with short tandem repeat (STR) markers revealed positive linkage to MCDR1. Two-point lod scores for marker D6S1284 and D6S1717 were 3.13 and 3.31 respectively. Within the minimal genetic interval, we identified and characterized a novel G-protein coupled receptor (GPCR) gene. Due to its high expression in the retina and functional importance of GPCR, this gene was considered as an attractive candidate. Sequencing of 5 exons of the gene did not reveal any mutational changes. Conclusion:We have identified a family linked to MCDR1 and excluded a candidate gene within the disease interval. MCDR1 shares important clinical features with AMD, such as macular drusen and choroidal neovascularization. Identification of the causative gene for MCDR1 will further our understanding of the pathogenesis of this disease and AMD.
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