Childhood glaucoma is characterized by progressive and irreversible damage to retinal ganglion cells and may lead to blindness. Disease classification distinguishes primary congenital glaucoma (PCG) and juvenile open angle glaucoma (JOAG) from secondary types of glaucoma depending on the presence of acquired/ non-acquired ocular or systemic features.
Whole-exome sequencing and copy number variation (CNV) analysis were performed in a Swiss cohort of 18 patients from 14 unrelated families.
The diagnosis of primary congenital glaucoma was established in 14 patients, six of which (43%) revealed pathogenic variants in CYP1B1, one (7%) frameshift variant in FOXC1, and seven (50%) remained without a significant genetic finding. Three patients were diagnosed with glaucoma associated with nonacquired ocular anomalies, of which two patients with mild ocular features of Axenfeld-Rieger syndrome were carrying a FOXC1 duplication plus an additional FOXC1 missense variant, and one patient with a Barkan membrane remained without genetic diagnosis. The diagnosis of juvenile open-angle glaucoma was apparent in one patient and genetic analysis revealed a FOXC1 duplication.
In summary our study revealed that DNA sequence analysis of CYP1B1 and FOXC1, as well as analysis of CNVs in FOXC1, should be performed before extended gene panel sequencing.
Wolfgang Berger (PhD)
David Grubich Atac (MD/PhD)
Samuel Koller (PhD)
Christina Gerth-Kahlert (MD), Dept. Ophthalmology, University Hospital Zurich
Elena Lang (MD), Dept. Ophthalmology, University Hospital Zurich