Whole genome sequencing of 10 families with optic disc drusen.

Introduction: Optic disc drusen (ODD) are believed to have a genetic predisposition, with autosomal dominant inheritance pattern with incomplete penetrance suggested through family pedigree analysis. ODD prevalence is higher in certain genetic disorders, such as pseudoxanthoma elasticum and retinitis pigmentosa. This study aimed to identify candidate genes potentially involved in the development of ODD.

Methods: Family members aged 18 years or older from families with ODD were included. Participants underwent optical coherence tomography of the optic nerve head, and blood samples were collected for whole-genome sequencing using the Illumina NovaSeq 6000 platform. Single nucleotide variants were identified with the Genome Analysis Toolkit (GATK) and filtered in VarSeq using a population frequency threshold of 1%. Selected genes were classified according to ACMG guidelines.

Results: A total of 10 families were included, three of which had more than two affected members. Thirty-three variants were identified, with the following genes selected for description: ABCC6, DDX50, TREX1, PLCB4, PTPRQ, LBR, RP1L1, and KRT3. The identified candidate genes showed a wide range of functions and are associated with different disorders. Of particular interest is ABCC6, which normally inhibits ectopic calcification.

Conclusion: We identified a list of candidate genes. Studies including larger ODD families are necessary to identify robust candidate genes.