Published online Jan 26, 2021. doi: 10.12998/wjcc.v9.i3.697
Peer-review started: September 14, 2020
First decision: November 20, 2020
Revised: November 26, 2020
Accepted: December 6, 2020
Article in press: December 6, 2020
Published online: January 26, 2021
Juvenile-onset primary open-angle glaucoma (JOAG), characterized by severe elevation of intraocular pressure and optic neuropathy prior to the age of 40, is a rare subtype of primary open-angle glaucoma. Several genetic mutations have been associated with JOAG.
The proband patient was a young male, diagnosed with primary open-angle glaucoma at the age of 27. The patient and his unaffected parents who have been excluded from classic genetic mutations for primary open-angle glaucoma were included to explore for other possible genetic variants through whole genome sequencing and bioinformatics analysis. In this trio, we found two heterozygous variants inherited from the parents in the proband: c.281G>A, p.Arg94His in OLFM2 and c.177C>G, p.Ile59Met in SIX6. Both genetic mutations are predicted through bioinformatics analysis to replace evolutionary conserved amino acids, therefore rendering a pathogenic effect on proteins. In contrast, very low frequencies for these genetic mutations were recorded in most common control databases.
This is the first report on coinherited mutations of OLFM2 and SIX6 in a JOAG family, which shows the complexity of JOAG inheritance. Large-scale clinical screening and molecular functional investigations on these coinherited mutations are imperative to improve our understanding of the development of JOAG.
Core Tip: This report describes a case of juvenile-onset primary open-angle glaucoma (JOAG) with a coinheritance of OLFM2 and SIX6 variants, which might contribute to the onset of JOAG. This finding may enrich the genetic spectrum of JOAG and prompt us to further investigate the functional effects of the two variants on JOAG.