Biallelic Variants in EPHA2 Identified in Three Large Inbred Families with Early-Onset Cataract.

Hereditary congenital cataract (HCC) is clinically and genetically heterogeneous. We investigated HCC that segregates in three inbred families (LUCC03, LUCC16, and LUCC24). Ophthalmological examinations revealed cataracts with variability related to the age of onset segregating in a recessive manner in these families. Exome sequencing of probands identified a novel homozygous c.2710delG;p.(Val904Cysfs*36) EPHA2 variant in LUCC03 and a known homozygous c.2353G>A;p.(Ala785Thr) EPHA2 variant in the other two recessive families. EPHA2 encodes a transmembrane tyrosine kinase receptor, which is primarily involved in membrane-transport, cell-cell adhesion, and repulsion signaling processes. Computational structural modeling predicts that substitution of a threonine for an alanine p.(Ala785Thr) results in the formation of three new hydrogen bonds with the neighboring residues, which causes misfolding of EPHA2 in both scenarios. Insights from our study will facilitate counseling regarding the molecular and phenotypic landscape of EPHA2-related HCC.

Association of single nucleotide polymorphism variations in CRYAA and CRYAB genes with congenital cataract in Pakistani population.

Background: The purpose of present study was to analyze the association of single nucleotide polymorphism (SNPs) variant in CRYAA and CRYAB genes with Congenital Cataract. Method: Total 196 blood samples of children were collected, out of which 102 samples were congenital cataract (case group) and 94 samples were normal individuals (control group). Genomic DNA was extracted by using optimized inorganic method. Tetra primers for SNPs were designed and TETRA-ARMs assay was performed on both groups. Genotypic, allelic frequency and haplotype analyses were obtained by using SNPstats software. Results: The coordination of genotypic and allelic frequencies of CRYAA and CRYAB genes variants and the association between case and control groups showed increased risk of congenital cataract in children who contained rs13053109 G > C variant of CRYAA in all models (all P > 0.05). This depicts the evident difference between the frequencies of case and control groups. The haplotype analysis of SNPs rs3761382, rs7278468 and rs13051039 of CRYAA gene showed weak linkage disequilibrium between the 3 SNPs (r2 < 0.8). The haplotype CTC indicated the high risk of congenital cataract in infants based of its p value (OR = 1.60 95% CI = 0.11-22.64, P > 0.05). Conclusion: The variation in CRYAA gene can be the risk factor for congenital cataract in infants.