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Abstract #90209 Published in IGR 21-3
Exome Sequencing in a Swiss Childhood Glaucoma Cohort Reveals and Variants as Most Frequent Causes
Lang E; Koller S; Bähr L; Töteberg-Harms M; Atac D; Roulez F; Bahr A; Steindl K; Feil S; Berger W; Gerth-Kahlert CTranslational vision science & technology 2020; 9: 47
PURPOSE: The aim of this study was to investigate the molecular basis of childhood glaucoma in Switzerland to recommend future targeted genetic analysis in the Swiss population. METHODS: Whole-exome sequencing and copy number variation (CNV) analysis was performed in a Swiss cohort of 18 patients from 14 unrelated families. Identified variants were validated by Sanger sequencing and multiplex ligation-dependent probe amplification. Breakpoints of structural variants were determined by a microarray. A minigene assay was conducted for functional analysis of a splice site variant. RESULTS: A diagnosis of primary congenital glaucoma was made in 14 patients, of which six (43%) harbored pathogenic variants in , one (7%) a frameshift variant in , and seven (50%) remained without a genetic diagnosis. Three patients were diagnosed with glaucoma associated with nonacquired ocular anomalies, of which two patients with mild ocular features of Axenfeld-Rieger syndrome harbored a duplication plus an additional missense variant, and one patient with a Barkan membrane remained without genetic diagnosis. A diagnosis of juvenile open-angle glaucoma was made in one patient, and genetic analysis revealed a duplication. CONCLUSIONS: Sequencing of and as well as analysis of CNVs in , should be performed before extended gene panel sequencing. TRANSLATIONAL RELEVANCE: The identification of the molecular cause of childhood glaucoma is a prerequisite for genetic counseling and personalized care for patients and families.
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Classification:
9.1.2 Juvenile glaucoma (Part of: 9 Clinical forms of glaucomas > 9.1 Developmental glaucomas)
3.5 Molecular biology incl. SiRNA (Part of: 3 Laboratory methods)
