Journal article
Exome Sequencing in a Swiss Childhood Glaucoma Cohort Reveals CYP1B1 and FOXC1 Variants as Most Frequent Causes
Translational vision science & technology, Vol.9(7), pp.47-12
06/30/2020
DOI: 10.1167/tvst.9.7.47
PMCID: PMC7414719
PMID: 32832252
Abstract
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.
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.
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.
Sequencing of
and
as well as analysis of CNVs in
, should be performed before extended gene panel sequencing.
The identification of the molecular cause of childhood glaucoma is a prerequisite for genetic counseling and personalized care for patients and families.
Details
- Title: Subtitle
- Exome Sequencing in a Swiss Childhood Glaucoma Cohort Reveals CYP1B1 and FOXC1 Variants as Most Frequent Causes
- Creators
- Elena Lang - University Hospital of ZurichSamuel Koller - University of ZurichLuzy Bähr - University of ZurichMarc Töteberg-Harms - University Hospital of ZurichDavid Atac - University of ZurichFrançoise Roulez - University Hospital of BaselAngela Bahr - University of ZurichKatharina Steindl - University of ZurichSilke Feil - University of ZurichWolfgang Berger - University of ZurichChristina Gerth-Kahlert - University Hospital of Zurich
- Resource Type
- Journal article
- Publication Details
- Translational vision science & technology, Vol.9(7), pp.47-12
- DOI
- 10.1167/tvst.9.7.47
- PMID
- 32832252
- PMCID
- PMC7414719
- ISSN
- 2164-2591
- eISSN
- 2164-2591
- Language
- English
- Date published
- 06/30/2020
- Academic Unit
- Ophthalmology and Visual Sciences
- Record Identifier
- 9984696717602771
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