The introduction of genomic testing into prenatal care has come at a rapid pace and has been met with significant clinical and ethical challenges, specifically when dealing with incidental findings. We present the case of a couple in their first pregnancy who were referred to our institution with isolated fetal cataracts on morphology scan. After an unremarkable infectious disease workup and microarray on an amniocentesis sample, the couple opted for fetal whole-exome sequencing to investigate the cataracts further. This investigation did not find any cause for the cataracts but yielded an incidental finding of a de novo pathogenic variant in the SCN1A gene unrelated to the cataracts. Pathogenic variants in the SCN1A gene are strongly associated with severe myoclonic epilepsy of infancy, or Dravet syndrome. After extensive genetic counseling, the couple decided to terminate the pregnancy at 28 weeks\' gestation based on this finding. This case highlights some of the important clinical and ethical considerations in prenatal genetic diagnosis, particularly in the group of patients in which there is no phenotypic evidence in-utero of the incidental finding. The case demonstrates the value of frameworks and guidelines to guide management decisions for both clinicians and patients.

The aim of our research was to examine the impact of a patient education program for parents of children with congenital cataract on parental stress, comprehension of disease information and parental satisfaction.
This prospective study included 177 parents of children with congenital cataract. The children were randomized into the following groups: the health education program with a multifaceted, interactive approach and conventional follow-up. Self-administered questionnaires were used for parental evaluation before and after the education program. The anxiety level, parental satisfaction and comprehension of the information were evaluated at each time point.
A multifaceted, interactive approach to education significantly reduced parental levels of anxiety compared with the conventional group (effect sizes: Parenting Stress Index, ƞ2 = 0.285; Ocular Treatment Index, ƞ2 = 0.346). This approach also improved comprehension-memorization scores (effect sizes: ƞ2 = 0.303) and parental satisfaction (p < 0.001). The impact of this new intervention was maintained for 6 and 12 months after the course.
The interactive, multifaceted education approach could efficiently improve the comprehension of disease-related information and parental satisfaction, resulting in significantly decreased parental anxiety.
This new patient education approach had a significant impact on congenital cataracts and may be generalized to other pediatric diseases.

Single point mutants of human γS-crystallin cause dominant congenital cataracts, a recent one of which involves the substitution of highly conserved glycine at 57th position with a bulkier tryptophan. Our high-resolution 3D structure of this G57W mutant (abbreviated hereafter as γS-G57W), reported recently revealed site-specific structural perturbations with higher aggregation and lower stability compared to its wild-type; a structural feature associated with important functional and therapeutic consequences. In this communication, we report for the first time, residue resolved conformational dynamics in both γS-WT and γS-G57W using solution NMR spectroscopy, and suggest how these differences could crucially affect the biochemistry of the mutant. Guided by our critical structural investigations, extensive conformational dynamics and biophysical studies presented here show that loss of structural stability arises from enhanced dynamics in Greek key motif 2 inducing flexibility in the N-terminal domain as opposed to its structurally unperturbed C-terminal counterpart. NMR spectral density correlations and internal dynamics comparisons with the wild-type suggest that the overall thermodynamic instability propagates from the mutated N-terminal β4-β5 loop providing a residue level understanding of the structural changes associated with this early onset of lens opacification. Our results highlight the vital role of conserved Greek key motifs in conferring structural stability to crystallins and provide crucial molecular insights into crystallin aggregation in the eye lens, which triggers cataract formation in children. Overall, this critical study provides a residue level understanding of how conformational changes affect the structure and function of crystallins in particular and proteins in general, during health and disease.