Investigation of a potential cone–survival factor gene in retinal disease.

Abstract

Abstract: : Purpose: A novel gene, CSF2A (lab acronym), shares homology to a recently discovered cone photoreceptor–survival factor (personal communication) and contains the same functional protein domains suggesting it may have a similar role. In addition, expression data examining the retinae of WT and rd1 mice indicate they share similar expression profiles making CSF2 an excellent candidate for retinal degeneration. CSF2 has been screened in a panel of autosomal recessive retinitis pigmentosa (arRP) and cone–rod dystrophy (CRD) patients to investigate it as a candidate for retinal disease. Methods: All exons and flanking intron boundary sequence of CSF2A in 69 CRD and 123 arRP index patients were screened for mutations by PCR and direct sequencing. Results: The coding sequence of CSF2A encodes a protein of 136 amino acids and the gene extends over 40kb of genomic DNA. A heterozygous silent change TTC>TTT (Phe33Phe) was found in exon 1 in one individual and another heterozygous silent change ACG>ACA (Thr53Thr), also in exon 1, was found in 3% of those screened. Conclusions: No coding changes in the nucleotide sequence of CSF2A was found in our cohort of patients analysed. Although no pathological mutations were identified so far, it is possible that this gene may cause a form of retinal disease not included in our data set, also mutations in promoter or intron sequences may have been missed. Screening of an autosomal dominant RP panel of patients is ongoing. Further characterisation of the transcript is underway to examine its role in cone–survival.

Keywords: candidate gene analysis • gene screening • degenerations/dystrophies