Abstract
Purpose: :
Retinitis pigmentosa (RP), the most prevalent group of inherited retinopathies, is associated with extensive genetic heterogeneity. Autosomal dominant RP accounts for approximately 40% of all inherited cases and can be caused by mutations in at least 15 different known genes. Mutation in Rhodopsin and peripherin/RDS genes are among the commonest causes of autosomal dominant RP. The purpose of this study was to identify causal mutations in the rhodopsin and peripherin/RDS genes in Mexican families with autosomal dominant RP.
Methods: :
Autosomal dominant RP was unambiguously identified by genealogy in 18 Mexican families. Diagnosis was made by a retina specialist by a complete ophthalmological examination and supported with fluorescein retinal angiography and electroretinogram. All subjects underwent systemic evaluation by a geneticist to identify systemic abnormalities and hereditary pattern. Genomic DNA was extracted from leukocytes of the peripheral blood and all exons of the rhodopsin and peripherin/RDS genes were amplified by PCR. Direct sequencing of PCR amplified products was performed using the Big Dye Terminator Cycle Sequencing kit. Samples were run in an ABI Prism 310 Genetic Analyzer.
Results: :
Four point heterozygous mutations were identified in the rhodopsin gene: a change from C to G at codon 58 that originates a substitution from threonine to arginine (family 3); a mutation from T to C at codon 45 that originates a change from phenylalanine to leucine (family 7); a transition from C to T at codon 135 that predicts a change from arginine to tryptophan (family 16) and a novel mutation from A to G at codon 122 that originates a replacement from glutamic acid to glycine (family 17). A striking intrafamilial clinical variation was observed in subjects carrying the novel Glu122Arg mutation. Interestingly, rhodopsin amino acid residue at position 122 has been demonstrated to be a functional determinant of rod and cone visual pigments. In the 14 families negative for rhodopsin mutations, genetic analysis of the Peripherin/RDS gene did not evidence deleterious mutation in any affected subject.
Conclusions: :
Three previously reported and a novel Glu122Arg mutation in rhodopsin gene were identified in this study. Our results expand the mutational spectrum of rhodopsin and adds to the genotype-phenotype correlation in rhodopsin-related RP. Peripherin/RDS mutations appears to be an uncommon cause of autosomal dominant RP in Mexico.
Keywords: retinal degenerations: hereditary • gene screening • genetics