Abstract
Abstract: :
Purpose: Firstly, to investigate the inheritance pattern and detailed clinical phenotype within a family with PPRCA. Secondly, to determine whether mutations within a number of known candidate genes associated with retinal degeneration segregate with the phenotype. Methods: A 28 year old male was referred for evaluation of a pigmentary retinopathy. A diagnosis of PPRCA with optic disc drusen was made. The patient was asymptomatic at the time of referral, however he subsequently suffered serious decline in visual function over the next 3 years. All family members had ophthalmic examination and fundus photography. Where there was doubt about the diagnosis full field electroretinography was performed. PCR amplification and DNA sequence analysis of mutational hotspots within candidate genes previously associated with retinal degeneration were undertaken. Sequence variations detected were tested for segregation with the PPRCA phenotype. Results:The patient’s father was unaffected, but although his mother and two siblings were asymptomatic they showed chorioretinal atrophy in the inferior quadrant and some mild paravenous pigmentary changes. Expression of the phenotype was found to be more severe in males as previously reported elsewhere. A heterozygous single nucleotide variation resulting in an amino acid change was found within the CRB1 gene, which co–segregated with affected family members. This variation was not detected in more than 100 unaffected individuals screened. A second sequence variation previously reported within RP3 to be non–pathogenic, was also found to co–segregate with affected family members. Conclusions: The CRB1 gene has been previously implicated in Leber’s congenital amaurosis and retinitis pigmentosa and a novel sequence variation has now been identified as a potential cause of PPRCA. This family shows an autosomal pattern of inheritance with variable expressivity, which appears to be sex influenced. The phenotypic variation is in keeping with other reports of PPRCA. The presence of an additional sequence change in the X–linked RP3 gene is interesting in view of the less severe expression of the phenotype in females.
Keywords: retinal degenerations: hereditary • gene screening • mutations