Screening for mutations in RPGR and RP2 genes in Jordanian families with X-linked retinitis pigmentosa

Abstract

ABSTRACT. Retinitis pigmentosa (RP) is a clinically and genetically heterogeneous disease causing progressive degeneration of retinal photoreceptor cells. X-linked RP (XLRP), in which photoreceptor degeneration begins in early childhood and complete blindness often occurs by the fourth decade of life, constitutes the most severe form of this disease. Two genes commonly associated with XLRP have previously been cloned: retinitis pigmentosa GTPase regulator (RPGR) and retinitis pigmentosa 2 (RP2). We sought to identify mutations in these genes in Jordanian families suffering from this disease. Five unrelated Jordanian families with confirmed XLRP were screened for such mutations using direct sequencing. Three mutations were identified in the ORF15 exon of RPGR. The silent g.ORF15+470G>A substitution and the g.ORF15+1822insA insertion in the 3ꞌ-untranslated region were found in both normal and affected male family members at comparable frequencies, and thus were considered normal variants. The third mutation, g.ORF15+588G>A, in which alanine is substituted by threonine, was found in all affected men and one unaffected man in the two families harboring this variant. Thus, this mutation may be pathogenic, but with incomplete penetrance. No RP2 mutations were found among the examined families. Mutation screening of RP patients is essential to understand the mechanism behind this disease and develop treatments. A complete family history is required to identify its inheritance pattern and provide genetic counseling for patients and their families.

Recent Developments on the major genes involved in retinitis pigmentosa

“…10 Similarly, there are xlRP cases among Jordanian, Japanese or patients of other ethnicities with diseasecausing mutation in RP2 or RPGR. 20,26 RPGR gene mutation may also cause LCA or RP of early onset, whereas in other benign cases visual acuity was stable until the age of forty. 27 Males appear with nyctalopia and visual impairment, while carrier females have milder phenotypes, mainly characterized by various degrees of myopia.…”