Investigation of the relationship between retinitis pigmentosa and bipolar disorder

Retinitis pigmentosa (RP) is a progressive form of visual loss caused by photoreceptor cell death and retinal pigment epithelial atrophy and is the most common type of genetically heterogeneous retinal dystrophy. The worldwide prevalence of RP is considered to be 0.25%. Bipolar disorder (BD) is a chronic and genetically heterogeneous mood disorder characterized by alternating episodes of manic, hypomanic and depression as a result of structural and functional changes in the brain. The worldwide prevalence of BD is considered to be 0.1%. The molecular pathology of these two disorders has not yet been definitively elucidated. Retina and brain have a common embryologic origin. There are genome-wide association studies (GWAS) suggesting that retinal degenerations and different neurodegenerative diseases may be related. The presence of cases with both RP and BB diseases suggests that these diseases may have common molecular pathologies. In our study, genotyping was performed by whole exome sequencing (WES) method in a sample of 10 individuals from three unrelated families in which these diseases cluster in order to reveal possible genotypes with overlapping genetic backgrounds that may have an effect on the etiology of both RP and BB diseases. WES analysis identified 15 variants and genotype-phenotype correlation was performed. Four of these variants are known to be pathogenic. One of the pathogenic variants was the c.1033G>A variant in the RHO gene, which has been associated with the RP phenotype, and three were KCNN2:c.2005C>T, PAH:c.782G>A, DMD:c.3G>A variants belonging to genes previously associated with different pathological phenotypes. The other 11 variants were evaluated as VUS in the databases. Five of these variants were novel and were detected in DCC, RP1L1, CACNA1C, TNNT3, CHM genes. The pathogenic RHO:c.1033G>A:p.val345met variant, which we think may affect RP and BB simultaneously, constitutes the most important finding of our study. Our study is the first study to evaluate whether there is a common genetic factor in the etiology of RP and BB diseases through WES analysis. Our results provide the literature with data that will contribute to the elucidation of the genetic basis of these two diseases and the establishment of integrative health practices.