Erratum: Glaucoma spectrum and age-related prevalence of individuals with FOXC1 and PITX2 variants

Abstract

Variation in FOXC1 and PITX2 is associated with Axenfeld-Rieger syndrome, characterised by structural defects of the anterior chamber of the eye and a range of systemic features. Approximately half of all affected individuals will develop glaucoma, but the age at diagnosis and the phenotypic spectrum have not been well defined. As phenotypic heterogeneity is common, we aimed to delineate the age-related penetrance and the full phenotypic spectrum of glaucoma in FOXC1 or PITX2 carriers recruited through a national disease registry. All coding exons of FOXC1 and PITX2 were directly sequenced and multiplex ligation-dependent probe amplification was performed to detect copy number variation. The cohort included 53 individuals from 24 families with disease-associated FOXC1 or PITX2 variants, including one individual diagnosed with primary congenital glaucoma and five with primary open-angle glaucoma. The overall prevalence of glaucoma was 58.5% and was similar for both genes (53.3% for FOXC1 vs 60.9% for PITX2, P = 0.59), however, the median age at glaucoma diagnosis was significantly lower in FOXC1 (6.0 ± 13.0 years) compared with PITX2 carriers (18.0 ± 10.6 years, P = 0.04). The penetrance at 10 years old was significantly lower in PITX2 than FOXC1 carriers (13.0% vs 42.9%, P = 0.03) but became comparable at 25 years old (71.4% vs 57.7%, P = 0.38). These findings have important implications for the genetic counselling of families affected by AxenfeldRieger syndrome, and also suggest that FOXC1 and PITX2 contribute to the genetic architecture of primary glaucoma subtypes.

Congenital glaucoma with anterior segment dysgenesis in individuals with biallelicCPAMD8variants

“…Within the limits of available patient data (four known CPAMD8 cases with glaucoma, plus four without glaucoma), we estimate glaucoma penetrance in CPAMD8 -related ASD to be ~50% (4/8), which is similar to more reliable estimates in ARS 17,18 .…”

“…The most common ASD presentation is Axenfeld-Rieger anomaly, known as Axenfeld-Rieger syndrome (ARS) when associated with systemic features. Individuals with ARS have a 50-60% lifetime risk of developing glaucoma, which can occur as early as the first year of life (Shields 1983;Souzeau 2017). …”

A novel variant in FOXC1 associated with atypical Axenfeld-Rieger syndrome

“…Patients may develop into glaucoma at a very young age, or they may be asymptomatic for a long time from childhood to youth until high intraocular pressure occurs. It is reported that more than 50% patients with FOXC1 -related ARS will develop into glaucoma eventually and the median onset age of glaucoma diagnosis is 6 ± 13.0 years [ 3 , 24 , 25 ]. In this study, although the 5-year-old boy had normal intraocular pressure and there were no alterations of the optic nerve, he is still at high risk of developing glaucoma.…”

“…Approximately 50% of ARS patients will develop into glaucoma, with an age of onset ranging from birth to late in adulthood [ 1 , 2 ]. Onset of glaucoma typically occurs before the teenage years [ 3 ].…”

Expression Analysis of the PITX2 Gene and Associations between Its Polymorphisms and Body Size and Carcass Traits in Chickens

“…Recently, polymorphism studies of the PITX2 gene were carried out on humans and mainly focused on its associations with diseases [22][23][24]. In livestock, polymorphisms of the PITX2 gene have been reported to be related to the milk traits of dairy goats and the meat quality and growth of pigs [25][26][27].…”