Analysis of glaucoma genes in Finnish patients with juvenile open‐angle glaucoma

Abstract

AbstractPurpose: Juvenile open‐angle glaucoma (JOAG) is a rare type of glaucoma diagnosed between the age of 4 and 40 years. Predisposition to JOAG is often inherited as a Mendelian autosomal dominant pattern. Pathogenic myocilin (MYOC) variants are reported in 8%–36% of patients but rarer variants in other genes could also predispose to JOAG. We investigated germline variants in known glaucoma genes in Finnish patients with JOAG.Methods: Finnish patients with JOAG treated between 2010 and 2018 at the Department of Ophthalmology, Helsinki University Hospital, Finland, were enrolled in the study. We sequenced all exonic regions and flanking splice sites of MYOC for six patients and one healthy relative using Sanger sequencing. In 55 patients, we performed exome sequencing to investigate variants also in 26 other glaucoma genes.Results: A total of 61 patients with JOAG from 58 pedigrees, and one healthy relative, were included. The mean [SD; range] age at diagnosis was 31.9 [7.5; 11–39]. Eight subjects (13.8%) had a normal‐tension disease, while 50 individuals (86.2%) had a disease with elevated intraocular pressure. Five probands had probable pathogenic variants in MYOC: c.1102C > T p.(Gln368Ter), c.1109C > T p.(Pro370Leu), c.1130C > T p.(Thr377Met), c.1132G > A p.(Asp378Asn), and c.1456C > T p.(Leu486Phe). Four of these patients had a family history of dominantly inherited JOAG. One patient and his mother with JOAG had a novel loss‐of‐function variant in the FOXC1 gene, c.366G > A p.(Trp122Ter). A patient with sporadic JOAG had a homozygous likely pathogenic variant in the LTBP2 gene, c.3938G > A p.(Cys1313Tyr). The frequency of MYOC variants was 8.6% (5/58). The genetic variants explained 12.1% (7 out of 58; 95% CI, 6.0%–22.8%) of JOAG in our cohort.Conclusions: The prevalence of pathogenic variants in known glaucoma genes is low in Finnish patients with JOAG. Due to the specific population history of Finland, it might be possible to identify novel glaucoma genes in the future.