The time of onset of inherited cataract

Abstract

Abstract Purpose The lens grows by addition of fibres to its surface, with the newest fibres just under the epithelium anteriorly and the capsule posteriorly. In slit‐section the cortex shows 4 optical zones of dysjunction (C1 to C4) with differing light‐scattering properties. We explore the clock‐like implications of this arrangement and how the spatiotemporal distribution of opacities implies the timing of mutated gene expression and/ or the influence of modifying factors. Methods Methods: A case report, literature review and proposal of a hypothesis Results We have observed dot cataract in a mother (42 years) and 2 sons (16 and 11 years) expressing a dominantly inherited, activating mutation of the calcium sensing receptor (CaSR). In each patient, lens opacities were present in the deep and superficial cortex (C2, 3 and 4) but absent from C1 and lens nucleus. Conclusion In our family, absence of opacities in the lens nucleus implies either that the mutated gene is not expressed pre‐natally or that there is protection from the effects of the mutation in utero, which is lost post‐natally. Absence of opacities in C1 implies the same for these young fibres and suggests that expression of disease (lens opacity) does not occur immediately after birth. We hypothesise that in our family, the expression of lens opacities once these fibres have entered C2, may be related to the switch from aerobic to anaerobic metabolism in the transitions from C1 to C2, to denucleation and loss of organelles and to other structural and functional changes which occur in this region. We suggest that the location and timing of appearance of inherited cataracts is related to the onset of gene expression and the presence of modulating factors which influence the effects of the mutated protein.