Genetic Modifiers of Non-Penetrance and RNA Expression Levels in PRPF31 -Associated Retinitis Pigmentosa in a Danish Cohort.

(1) Background/aims: To examine potential genetic modifiers of disease penetrance in -associated retinitis pigmentosa 11 (RP11). (2) Methods: Blood samples from individuals (n = 37) with variants believed to be disease-causing were used for molecular genetic testing and, in some cases (n = 23), also for mRNA expression analyses. Medical charts were used to establish if individuals were symptomatic (RP) or asymptomatic non-penetrant carriers (NPC). RNA expression levels of and were measured on peripheral whole blood using quantitative real-time PCR normalized to . Copy number variation of minisatellite repeat element 1 (MSR1) was performed with DNA fragment analysis. (3) Results: mRNA expression analyses on 22 individuals (17 with RP and 5 non-penetrant carriers) revealed no statistically significant differences in or mRNA expression levels between individuals with RP and non-penetrant carriers. Among 37 individuals, we found that all three carriers of a 4-copy MSR1 sequence on their wild-type (WT) allele were non-penetrant carriers. However, copy number variation of MSR1 is not the sole determinant factor of non-penetrance, as not all non-penetrant carriers carried a 4-copy WT allele. A 4-copy MSR1 mutant allele was not associated with non-penetrance. (4) Conclusions: In this Danish cohort, a 4-copy MSR1 WT allele was associated with non-penetrance of retinitis pigmentosa caused by variants. The level of mRNA expression in peripheral whole blood was not a useful indicator of disease status.