Application of multi-gene panel in juvenile-onset glaucoma: report of 2 cases with dominant & recessive inheritance

Background and Aim : Glaucoma is the leading cause of preventable irreversible blindness worldwide. Primary open-angle subtype (POAG) can be subclassified to congenital (before 4 yr), juvenile (4 to 40 yr) or adult (after 40 yr) onset. Early-onset glaucoma more likely to be inherited in a Mendelian fashion, involving single genes, little influences from environmental factors. So, reproductive choices and interventions can significantly reduce its familial recurrence. Methods : Searching the annual registries of Shahrood genetic counseling centers, the index cases who had been reported to have glaucoma, were interviewed and if their disease began between 4 & 40 years of age, called for genetic study. Next generation sequencing (NGS) based test of more than 200 genes involved in visual disorders was done. The genetic test covered 7 genes documented in OMIM database, as causative for juvenile and/or congenital glaucoma, among others.Results : 2 unrelated affected patients were known and both participated: The first one, 46 year old male confronted with disease at 7 years of age; his 4th degree relative parents & all of his 5 sibs were healthy; but he reported glaucoma in two of his cousins. The second patient, 25 year old female with disease-onset about 5 years of age, had similarly affected father, paternal grandmother, and 2 of 3 (older) sibs. NGS revealed homozygous frame-shift previously reported (pathogenic) insertion mutation in the CYP1B1 gene, compatible with AR inheritance pattern deduced from family history. In the case of second case, in favor of AD inheritance presumption due to pedigree, a heterozygous, missense variant of the MYOC gene was recognized that because of its novelty, classified as variation of unknown significance. Conclusion : Detection of the causative mutation by genetic testing, could be expected and should be considered in the preventive approach to juvenile-onset open-angle glaucoma.