A decade of RAD51C and RAD51D germline variants in cancer.

Defects in DNA repair genes have been extensively associated with cancer susceptibility. Germline pathogenic variants (GPV) in genes involved in homologous recombination repair pathways predispose to cancers arising mainly in the breast and ovary, but also other tissues. The RAD51 paralogs RAD51C and RAD51D were included in this group 10 years ago when germline variants were associated with non-BRCA1/2 familial ovarian cancer. Here, we have reviewed the landscape of RAD51C and RAD51D germline variants in cancer reported in the literature during the last decade, integrating this list with variants identified by in-house patient screening. A comprehensive catalog of 341 variants that have been classified applying ACMG/AMP criteria has been generated pinpointing the existence of recurrent variants in both genes. Recurrent variants have been extensively discussed compiling data on population frequencies and functional characterization if available, highlighting variants that have not been fully characterized yet to properly establish their pathogenicity. Finally, we have complemented this data with relevant information regarding the conservation of mutated residues among RAD51 paralogs and modeling of putative hotspot areas, which contributes to generating an exhaustive update on these two cancer predisposition genes.

Diurnal Variations in Intraocular Pressure, Central Corneal Thickness, and Macular and Retinal Nerve Fiber Layer Thickness in Diabetics and Normal Individuals.

PURPOSE: To evaluate diurnal variations in intraocular pressure (IOP), central corneal thickness (CCT), and macular and retinal nerve fiber layer (RNFL) thickness in diabetic patients and normal individuals. METHODS: This study included 11 diabetic patients with macular edema and 11 healthy individuals. IOP, CCT, and macular and RNFL thickness were measured every 3 hours on a single day between 9 AM and 6 PM. Diurnal variations in IOP, CCT, total macular volume (TMV), central macular thickness (CMT), average macular thickness (AMT), and RNFL thickness were measured. RESULTS: None of the parameters showed a significant absolute or relative change over the course of the day. However, the following non-significant changes were observed. In the control group, all parameters demonstrated the highest values at 9 AM. The lowest IOP, TMV and AMT occurred at 12 PM; lowest CCT and RNFL at 6 PM; and the lowest CMT at 3 PM. Diabetic subjects had the highest values of RNFL, CMT and TMV at 9 AM, and that for IOP, CCT and AMT at 6 PM. The lowest RNFL and CMT values occurred at 6 PM; lowest IOP at 12 PM; and the lowest CCT, TMV and AMT were observed at 3 PM. In the diabetic group, TMV, CMT, AMT and CCT were significantly higher and RNFL was significantly lower than the control group at all time points (all P- values < 0.05). CONCLUSION: While there were slight decreases in IOP, RNFL thickness and CMT during the day, these changes were not significant between 9 AM and 6 PM and probably do not affect the interpretation of measurements.

Age-related variations in corneal biomechanical properties.

PURPOSE: To determine age-related changes in corneal viscoelastic properties in healthy individuals. METHODS: This observational cross-sectional study was performed at the Department of Ophthalmology, Imam Khomeini Hospital, Ahvaz, Iran and included 302 healthy individuals in 6 age decades (range: 10-69 years). After complete ocular examination, corneal viscoelastic properties were measured by ocular response analyzer and central corneal thickness (CCT) by an ultrasonic pachymeter. Our main outcome measures were corneal viscoelastic properties in different age groups. RESULTS: Corneal hysteresis (CH) and corneal resistance factor (CRF) showed a significant negative correlation with age (P < 0.001 for both, r = -0.353 and r = -0.246, respectively). Female gender had significantly higher CH (P = 0.017) and CRF (P = 0.019). CH and CRF were significantly correlated (P < 0.001, r = 0.821). CCT showed a biphasic pattern with significantly higher thicknesses before 20 and after 50 years of age. CH and CRF were significantly correlated with CCT (P < 0.001 for both, r = 0.21 and r = 0.26, respectively) and intraocular pressure (IOP) (P < 0.001 for both, r = -0.474 and r = 0.598, respectively). Corneal-compensated IOP (IOPcc) was significantly higher after age 40 compared to age group <20 (p < 0.045). Goldmann-correlated IOP (IOPg) was significantly correlated with CCT (P = 0.001, r = 0.193), while IOPcc showed no correlation with CCT (P = 0.265, r = 0.062). CH was significantly higher in hyperopic eyes compared to emmetropic eyes (P = 0.009) and myopic eye (P < 0.001). CONCLUSIONS: In this study, there was a decrease in CH and CRF with an increase in age. Hyperopia and female gender are associated with higher CH and CRF. CCT is higher toward the extremes of life and is significantly correlated with CH and CRF.