8 research outputs found

    Further evidence for an association of ABCR alleles with age-related macular degeneration. The International ABCR Screening Consortium

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    Age-related macular degeneration (AMD) accounts for >50% of the registered visual disability among North American and Western European populations and has been associated both with environmental factors, such as smoking, and with genetic factors. Previously we have reported disease-associated variants in the ABCR (also called ABCA4) gene in a subset of patients affected with this complex disorder. We have now tested our original hypothesis, that ABCR is a dominant susceptibility locus for AMD, by screening 1,218 unrelated AMD patients of North American and Western European origin and 1,258 comparison individuals from 15 centers in North America and Europe for the two most frequent AMD-associated variants found in ABCR. These two sequence changes, G1961E and D2177N, were found in one allele of ABCR in 40 patients (∼3.4%), and in 13 control subjects (∼0.95%). Fisher’s two-sided exact test confirmed that these two variants are associated with AMD at a statistically significant level (P<.0001). The risk of AMD is elevated approximately threefold in D2177N carriers and approximately fivefold in G1961E carriers. The identification of a gene that confers risk of AMD is an important step in unraveling this complex disorder

    Molecular genetic basis of primary inherited optic neuropathies

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    Aim To review the molecular genetic basis of primary inherited optic neuropathies. Methods Medline and Embase search. Results Inherited optic neuropathies are a genetically diverse group of disorders that present with reduced visual acuity and the clinical appearance of optic atrophy. The inherited optic neuropathies may be sporadic or familial, in which case the mode of inheritance may be Mendelian (autosomal dominant, autosomal recessive, X-linked recessive) or non-Mendelian (mitochondrial). Two genes for dominantly inherited optic atrophy have been mapped (OPA1 and OPA4), of which the gene has been identified in one (OPA1). A gene for recessive optic atrophy (OPA3) has also been identified. X-linked optic atrophy (OPA2) has been mapped but to date no gene has been identified. Mutations in mitochondrial DNA have been identified in Leber's hereditary optic neuropathy. Conclusions Mutations in genes from both the nuclear and mitochondrial genomes appear to be responsible. Mitochondrial dysfunction, in the broadest sense, is emerging as central to the pathogenesis of this group of conditions
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