Candidate gene screening for MCDR1 (North Carolina Macular Dystrophy).

Abstract

Abstract: : Purpose:We have carried out a candidate gene screening in families with MCDR1 for the GPR63 (belonging to a rodopsin like activity family of genes). MCDR1 is an autosomal dominant nonprogressive disease. The phenotype is characterized by bilaterally symmetrical but highly variable macular degeneration ranging from drusen to staphylomata. The peripheral retina can be variably abnormal. Light microscopy studies have demonstrated a discrete macular lesion characterized by focal absence of photoreceptors and retinal pigment epithelium with attenuation of the Bruch membrane and focal atrophy of the choriocapillaris. Adjacent to the macular lesion, some lipofuscin were also identified in the retinal pigment epithelium. GPR63 is located within the locus for MCDR1 on 6q16 and involved in the pathway for G protein coupled receptors. The G protein coupled receptor genes are know to be involved in retinal diseases. Interacting transporter proteins like ABCA4 are also known to cause retinal disease. Supporting evidence like the mouse homologue is also located in the syntenic region assigned to the disease.Methods: Candidate genes were carefully selected to support phenotypic and pathological changes in MCDR1 patients. Direct sequencing of the entire gene coding and non coding was carried out on more than 12 probands representing different families. Results: Although the gene represents a good candidate we did not observed any changes which segregated with the disease or was absent in control individuals. A 765 A>T change within the coding region of the gene did not segregate in the families and is considered a polymorphism. Conclusions: We rule out GPR63 as a candidate gene and present evidence to show that it is not directly involved in the etiology of the disease. However, changes within the intornic, regulatory region and splice variants cannot be ruled out.

Keywords: gene screening • macula/fovea • genetics