Abstract
Abstract: :
Purpose:Stargardt macular dystrophy (STGD) is the most common hereditary macular dystrophy and is characterized by decreased central vision in the 1st or 2nd decade of life, macular atrophy, and presence of yellow flecks in the posterior pole. In most instances STGD is inherited as an autosomal recessive or simplex trait. A recessive locus was assigned to chromosome 1p (STGD1, ABCA4 gene). Numerous families have been described in which features of STGD are transmitted in an autosomal dominant manner, and dominant loci have been mapped to chromosomes 6q (STGD3, ELOVL4 gene) and 4p (STGD4). We describe the effort to map a disease-causing gene in a large Greek family using genetic linkage analysis. Methods:Ophthalmoscopic examination, fundus photography, and fluorescein angiography were performed to identify individuals with STGD. Genomic DNA was obtained from the blood of 29 family members (11 affected, 18 unaffected) and was genotyped using polymorphic DNA markers. Results:We describe a large five-generation pedigree with dominant STGD from Epirus, Greece. The family consists of 234 individuals with 24 affected members. Clinical examination revealed visual acuity ranging from 20/25 to 20/200, with age at onset between 7 and 18 years. Fundoscopic examination showed loss of foveal reflex, "beaten bronze" appearance of the foveal region, and flecks of varying degrees. The disease was symmetric in the two eyes and progressive with age. Linkage analysis with short tandem repeat (STR) markers excluded linkage to known STGD loci, and a genomewide search is in progress. Conclusion:We have identified a family with an autosomal dominant STGD likely representing a new disease locus. Identification of another causative gene for STGD will aid in our understanding of the pathogenesis of this disease, and allow the investigation of therapeutic agents aimed at treating the underlying biochemical cause of Stargardt’s and other retinal dystrophies.
Keywords: 418 gene mapping • 457 linkage analysis • 420 genetics