Novel progressive rod-cone degeneration mutation causes retinitis pigmentosa

Retinitis pigmentosa (RP) is a genetic disorder often caused by single or multiple mutations. The progressive rod-cone degeneration (PRCD) gene is linked to retinal degeneration. This study identified a family affected by RP carrying a frameshift mutation (c.67del) in the PRCD gene. Blood samples from a patient with RP and three family members were analyzed by whole-exome sequencing. A point-mutant mouse model was created using gene-targeted modification to validate the suspected causative gene phenotypically. Binocular ophthalmological exams, including electroretinography and optical coherence tomography (OCT), were performed at P0, P30, P60, and P180. After 180 days, retinas were analyzed by polymerase chain reaction (PCR), Western blotting (WB) and immunofluorescence to measure gene expression and observe phenotypical changes, respectively. We used whole-exome sequencing of peripheral blood to identify a novel frameshift mutation in the PRCD gene: c.67del (p.Val23SerfsTer31). This mutation introduces a premature termination codon at amino acid position 31. Predictive tools indicate that this mutation is likely pathogenic. The proband's parents are consanguineous; the mother is a heterozygous carrier; the remaining two living family members exhibit a wild-type genotype. PCR, WB and immunofluorescent staining revealed significantly low Prcd expression in the Prcd^-/- mice than in wild-type mice. OCT and visual electrophysiological assessments detected lesions in the fundus of Prcd^-/- mice eyes; the severity of pathological changes increased with age. This study discovered a new mutation in the RP-associated Prcd gene and confirmed that it causes retinopathy in Prcd^-/- mice.