Genetic variants through exome sequencing in Spanish patients affected by primary congenital glaucoma and juvenile...

To evaluate the genetic characteristics using whole-exome sequencing (WES), aiming to assess the potential of this approach for accurate diagnoses and to explore the genetic factors underlying these conditions.

A total of 28 patients, including 6 with primary congenital glaucoma and 22 with juvenile open-angle glaucoma, were studied. Genetic analysis involved initial Sanger sequencing for the CYP1B1 and MYOC genes. WES was subsequently performed in 11 patients with negative initial results, using a panel of genes most associated with glaucoma and related ophthalmic syndromes. Variant interpretation was performed based on American College of Medical Genetics and Genomics guidelines. Segregation analysis was performed when possible.

Pathogenic variants in CYP1B1 and MYOC genes were identified in three patients (10%). WES identified disease-causing variants in three additional patients (27% of those with negative results from the initial testing conducted so far), all of them with syndromic features. In families where segregation analysis was possible, variants were confirmed to segregate with the clinical presentation. The diagnostic yield was 21%.

WES is an effective diagnostic tool for early-onset glaucoma, enhancing clinical management and genetic counseling. It supports its use in routine diagnostics to enable early detection and intervention for at-risk relatives. Further research is needed to uncover additional genetic factors and refine testing guidelines.