Advanced in early‐ and adult‐onset glaucoma genetics

Glaucoma is a genetically and clinically heterogeneous disease that can affect individuals at all ages. Rare genetic variants are known to cause early‐onset glaucoma while common variants contribute to adult‐onset open angle glaucoma (POAG). Genome‐wide association studies (GWAS) are an effective approach for discovery genetic risk factors of diseases with complex inheritance such as the adult POAG. The International Glaucoma Genetics Consortium (IGGC) including investigators worldwide has collected over 50,000 POAG samples. The results of recent GWASs of the IGGC leading to the discovery of more than 50 genes will be discussed providing important novel insights into disease pathogenesis. For the early onset‐ and congenital glaucoma currently 9 genes are known and using these genes for genetic testing can inform genetic counseling and risk assessment. However, the diagnostic yield for these genes is less than the half of all early glaucoma implicating the contributions of additional genes. Whole exome sequencing (WES) has been revealed a useful approach for gene discovery particularly in smaller families leading, for example, to the identification of the novel ANGPT1‐TEK signaling pathway in primary congenital glaucoma. Interesting, using WES in our cohort of patients with early onset glaucoma we could identify mutations in different genes involved in others forms of glaucoma and anterior segment anomalies, thus helping not only to identify novel candidate genes but also helping to define the correct diagnosis. Interesting by large patients screening, some genes involved in early onset glaucoma forms, i.e. ANGPT1, contribute also to adult glaucoma.