Novel structural variant in CACNA1F causing congenital stationary night blindness identified with whole genome...

Infantile nystagmus syndrome is often the presenting symptom of an underlying retinal disorder, such as Congenital Stationary Night Blindness (CSNB). CSNB, an inherited retinal disorder affecting rod mediated "night" vision, has several known genetic causes. Despite advances in genetic testing, structural variants can be difficult to detect using traditional methods like whole exome sequencing.

We present a case involving a novel structural variant in CACNA1F, detected through whole genome sequencing (WGS), in an 8-year-old boy who initially presented with infantile nystagmus and high myopia. The CACNA1F variant consists of a 380 bp inverted duplication involving exons 41 and 42. Bioinformatics analyses predicted a cryptic exon insertion instead of exon 41, leading to 11 amino acids and a stop codon, resulting in protein truncation. PCR confirmed the presence of the duplication that is hemizygous in the proband and heterozygous in his carrier mother. Although highly myopic, she reports no night vision difficulties.

This case illustrates WGS's superior capacity to detect complex genomic rearrangements that conventional exome-focused or gene panel strategies may overlook. Our findings both expand the catalog of known pathogenic variants and underscore the role of WGS in genetic diagnosis.