A variant p.S45G at a conserved phosphorylation site of αA-crystallin in an Indian juvenile cortical cataract patient

The aim of study is to identify the potential genetic cause in a juvenile cortical cataract patient from a DNA sample. A young patient was enrolled in the current study and diagnosed with cortical cataract having blurred discomfort, poor night vision, and monocular diplopia by ophthalmic examination. DNA extraction was performed from peripheral blood, and all exons and exon–intron boundaries of three Crystallin genes, CRYAA , CRYAB , and CRYBB1 , were amplified using intron-specific primers by PCR, followed by resequencing through the Sanger method. Sanger sequencing revealed a heterozygous DNA variant, g.44589342A>G or c.133A>G (p.S45G), in exon 1 in CRYAA . This DNA variant was predicted to be disease causing by Mutation Taster and other prediction tools. Furthermore, Franklin ACMG classification predicted that the CRYAA: c.133A>G (p.S45G) genetic variant is a variant of uncertain significance. In silico analysis revealed that the protein position (S45) was evolutionarily conserved for serine and crucial for phosphorylation at this conserved site of CRYAA. The genetic variant p.S45G could alter the phosphorylation pattern of αA-crystallin in the juvenile cortical cataract patient. Finally, the genetic variant g.44589342A>G (p.S45G) was screened in 130 unrelated healthy controls in the Indian population, and the absence of this variant in healthy individuals suggests that p.S45G is a disease-causing factor or DNA variant for juvenile cortical cataract. The DNA variant CRYAA: c.133A>G (p.S45G) in the Crystallin Alpha A gene causes juvenile cortical cataract due to discrepancy in its phosphorylation pattern. Thus, the genetic variant p.S45G has been identified as a novel variant in juvenile cataract and is a second DNA variant identified in CRYAA that causes juvenile cataract.