Inherited macular disorders: is there any genetic similarity between early onset and late onset macular degenerations? [abstract]

ABSTRACT

Over the past 5 years, the genes responsible for several early-onset macular degeneration have been identified. Recent disorders include the genes responsible for autosomal recessive and dominant Stargardt disease, Sorsby fundus dystrophy, Best disease, and Mallatia Leventinese, also known as autosomal dominant drusen or Doyne honeycomb macular dystrophy. Significant attention has been focused on the gene responsible autosomal recessive Stargardt disease. Mutations in this gene, known as ABCA4 and formerly referred to as ABCR, are the most common cause of retinal degenerations so far identified. Different mutations in this gene have been associated not only with Stargardt disease, but also with cone-rod dystrophy, retinitis pigmentosa, and age-related macular degeneration (AMD). The relationship between the ABCA4 gene and AMD is highly controversial. The controversy is not whether AMD is an inherited disorder, but whether the ABCA4 gene plays a significant role in AMD inheritance. The data from population and family studies, particularly in identical twin studies, strongly support a role for heredity in AMD. Moreover, recent results from the Genetics of Age-Related Maculopathy (GARM) Study, a multicentre collaborative effort designed to identify the genes responsible for AMD, have revealed 6 chromosomal loci that are likely to contain the majority of genes responsible for AMD. The unexpected result from this study is that the genes responsible for the early-onset macular degenerations are not located at any of these chromosomal loci. Therefore, It seems likely that these early-onset genes will not have a significant role in causing the late-onset condition. (AU)