Purchase this article with an account.
Xueli Chen, Keri Allen, Kevin Linkroum, DanYi Wang, Mark Consugar, Elizabeth DelBono, Janey L Wiggs; FOXF2 mutations in patients with early-onset glaucoma. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2538.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
A Foxf2 missense allele is associated with anterior segment dysgenesis in a mouse model (McKeone et al., 2011); however mutations in humans with anterior segment dysgenesis and/or glaucoma have not yet been observed. The purpose of this study was to screen for deleterious mutations in FOXF2 early-onset glaucoma probands.
108 probands diagnosed with early-onset glaucoma (before the age of 40) without mutations in known early-onset glaucoma genes (CYP1B1, FOXC1, LTBP2, MYOC, PAX6, and PITX2) were enrolled. All FOXF2 coding exons were sequenced using Sanger sequencing. FOXF2 copy number variants (CNVs) were initially screened using Multiplex Ligation Probe Amplification (MLPA) (SALSA MLPA probemix P208-C1 Human Telomere-6, MRC Holland) and confirmed using custom aCGH microarray slides scanned on an Agilent Technologies SureScan microarray scanner.
One early-onset glaucoma proband was found to have a FOXF2 missense mutation (H430R) involving a highly evolutionarily conserved amino acid (GERP = 4.58). The missense change is rare (1/6,502 individuals) in the National Heart Lung Blood Institute Exome Sequencing Project (NHLBI ESP), and is predicted to be damaging by Polyphen2 (0.993). A sibling is also affected by glaucoma but was not available for screening. The patient was diagnosed with glaucoma at age 20 and does not have clinical evidence of anterior segment dysgenesis. A second early-onset glaucoma proband was found to have a novel FOXF2 duplication that involves the entire gene (248kb). Three other family members are affected and all 3 have the same novel FOXF2 duplication. The duplication was not present in any unaffected family members. All of the affected family members have early-onset glaucoma (range 5 months to 17 years) and also have varying degrees of iris stromal atrophy.
Results from this study suggest that mutations in FOXF2 can cause early-onset glaucoma in humans. Further studies to confirm these findings and define the role of FOXF2 in glaucoma would be of interest.
This PDF is available to Subscribers Only