Bulgarian Roma (Gypsy) Pedigree With Severe X–Linked Retinitis Pigmentosa

Abstract

Abstract: : Purpose: To identify the disease gene associated with a severe type of retinitis pigmentosa in a large Bulgarian Roma (Gypsy) pedigree. Methods: Standard ophthalmic examinations were used to diagnose retinitis pigmentosa in a large family with potentially a dominant mode of inheritance. All carrier females manifested clinical symptoms of RP although less severe than the males. 22 affected and 6 unaffected individuals were selected to perform linkage analysis. Fluorescently tagged ABI microsatellite markers have been initially used to exclude the family from all known autosomal dominant RP (adRP) loci. Additionally, due to a lack of male to male transmission, tetranucleotide markers tightly linked to RP2 (GATA144D04) and RP3 (DXS1068) were also tested. Results: All the markers linked to the known adRP loci gave significant negative lod scores, confirming exclusion of these adRP loci in the family. Subsequently X–linked inheritance was considered. Markers linked to RP2 and RP3 were used for linkage analysis. Close linkage to the XLRP region without recombination was observed in all affected individuals. Screening of the RP2 gene in affected individuals did not reveal a mutation. Work is ongoing for mutation screening of the RPGR (RP3) gene. Conclusions: This is the first large Bulgarian pedigree identified with retinitis pigmentosa. A possible mutation in an XLRP gene in this large endogamous group of Gypsy origin may indicate that XLRP is the predominant cause of RP within this population.

Keywords: retina • linkage analysis • candidate gene analysis