Abstract
Purpose: :
The macular dystrophies comprise a heterogeneous group of disorders characterized by early onset, progressive central visual loss and bilateral changes in the macula with central areolar choroidal atrophy. We identified a Chinese family with autosomal dominant macular dystrophy by clinical examination. The purpose of this study is to analyse the clinical features of the family and to identify its genetic entity by candidate gene approach and linkage analysis.
Methods: :
Fifety-two individuals in the family were investigated. Clinical examination included family and medical history, visual acuity, color vision, slit lamp micromoscopy, indirect ophthalmoscopy, color fundus photography, fluorescein angiography, automated perimetry, and electroretinography. The family was followed up for 30monthes. Genomic DNA was extracted from leukocytes of peripheral blood for all individuals of the family. Microsatellites covering the known genetic loci responsible for autosomal dominant macular dystrophies were analyzed by polymerase chain reaction(PCR). Linkage analysis was performed by MLINK program from LINKAGE package.
Results: :
Seven individuals with macular dystrophy were demonstrated in the family in three continuous generations. The disease was progressive, affecting both male and female. In the early stage of the disorder, patient showed relatively normal-appearing fundus with mild mottling of the pigment epithelium in the macular. As disease progressed, a bull’s eye maculopathy and central geographic atrophy were demonstrated. The peripheral retina was normal in all affected individuals. Fluorescein angiography revealed a bull’s eye-like hyperfluorescent area in the macula in the early stage and a transmission window defect due to retinal pigment epithelial atrophy intermingled with a hypofluorescent area of choriocapillaris atrophy in the advanced stage. Electroretinography revealed a mild reduction or appeared normal in the photopic amplitude. One affected male in the first generation was accompanied by late stage of chronic angle-closure glaucoma. Linkage analyses exculeds the known genes and loci, including GUCA1A, RDS, ELOVL4, RCD1, CDX, loci 17p13.2→17p13.1, and 4p15.2-4p16.3.
Conclusions: :
Central areolar choroidal dystrophy was shown in this family and severa genes and genetic loci were excluded to be responsible for the family. We confirmed the genetic heterogeneity of autosomal dominant macular dystrophy. Whole genome-scan should be carried out to identify genetic etity for the disease.
Keywords: linkage analysis • genetics • retinal degenerations: hereditary