A novel COL4A5 splicing variant in alport syndrome presenting with extreme myopia

This study aims to describe the diagnosis and management of a case with bilateral anterior lenticonus.

A comprehensive ophthalmological assessment was performed on the proband, including: ultrasound biomicroscopy (UBM), optical biometric measurement, fundus photography, optical coherence tomography (OCT), visual field testing, and pure-tone audiometry. The patient subsequently underwent phacoemulsification with intraocular lens (IOL) implantation. Immunofluorescence analysis was utilized to assess the expression of the α5 chain of type IV collagen in the lens capsule. Whole exome sequencing (WES) of the proband complemented by Sanger sequencing validation of the parents was conducted to identify potential pathogenic variants.

The proband exhibited binocular high myopia, with no significant improvement in visual acuity despite correction. UBM demonstrated anterior protrusion of the central lens area in both eyes. OCT revealed temporal retinal thinning in both eyes compared to the nasal retina. The corresponding protein was absent in the lens capsule of the proband. WES identified a novel variant (c.4821+2T>C: p.?) in the COL4A5 gene, and Sanger sequencing confirmed that the proband's mother was a carrier of this variant. The proband exhibited an absence of expression of the alpha 5 chain of type IV collagen (α5(IV)) in the lens capsule of the proband. Among various refractive calculation formulas, the aphakic formula demonstrated the smallest error.

A novel pathogenic COL4A5 splicing variant (c.4821+2T>C) was identified, which was associated with Alport syndrome. Furthermore, the aphakic formula may reduce refractive prediction error in cases of anterior lenticonus.