Early phenotypic features of aniridia-associated keratopathy and association with PAX6 coding mutations

Lagali, Neil; Wowra, Bogumił; Fries, Fabian N.; Latta, Lorenz; Moslemani, Kayed; Utheim, Tor Paaske; Wylęgała, Edward; Seitz, Berthold; Käsmann‐Kellner, Barbara

doi:10.1016/j.jtos.2019.11.002

Cited by 38 publications

(58 citation statements)

References 48 publications

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“…Accordingly, a recent report from Pedersen et al showed that family members with the same PAX6 mutation, a 2 bp deletion in intron 2, presented with variable iris involvement, which ranged from almost normal to no iris, as well as different degrees of foveal hypoplasia [115,116]. In contrast, Lagali et al recently found a correlation between PAX6 variants and the severity and progression of ARK [117,118]. In a cohort of 46 aniridia patients, the authors found a minimal level of keratopathy and an increase in cornea thickness in all aniridia patients from early age.…”

Section: Aniridia (Mim 106210)mentioning

confidence: 99%

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The Spectrum of PAX6 Mutations and Genotype-Phenotype Correlations in the Eye

Cunha¹,

Arno

Cortón

et al. 2019

Genes

133

107

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The transcription factor PAX6 is essential in ocular development in vertebrates, being considered the master regulator of the eye. During eye development, it is essential for the correct patterning and formation of the multi-layered optic cup and it is involved in the developing lens and corneal epithelium. In adulthood, it is mostly expressed in cornea, iris, and lens. PAX6 is a dosage-sensitive gene and it is highly regulated by several elements located upstream, downstream, and within the gene. There are more than 500 different mutations described to affect PAX6 and its regulatory regions, the majority of which lead to PAX6 haploinsufficiency, causing several ocular and systemic abnormalities. Aniridia is an autosomal dominant disorder that is marked by the complete or partial absence of the iris, foveal hypoplasia, and nystagmus, and is caused by heterozygous PAX6 mutations. Other ocular abnormalities have also been associated with PAX6 changes, and genotype-phenotype correlations are emerging. This review will cover recent advancements in PAX6 regulation, particularly the role of several enhancers that are known to regulate PAX6 during eye development and disease. We will also present an updated overview of the mutation spectrum, where an increasing number of mutations in the non-coding regions have been reported. Novel genotype-phenotype correlations will also be discussed.

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Section: Aniridia (Mim 106210)mentioning

confidence: 99%

“…Patients with missense mutations showed milder non-progressive ARK and, lastly, non-PAX6 mutations had the mildest forms of disease and generally the best visual acuity [117]. However, the clinical phenotype of ARK is heterogenous and patients with the same mutation can often display different degrees of ARK.…”

Section: Aniridia (Mim 106210)mentioning

confidence: 99%

The Spectrum of PAX6 Mutations and Genotype-Phenotype Correlations in the Eye

Cunha¹,

Arno

Cortón

et al. 2019

Genes

133

107

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“…The density of mature dendritic cells has been reported to be 10-20 times higher in aniridia subjects than in healthy individuals. 83 A significant correlation between increasing severity of AAK and a higher number of intraocular surgeries has been found. 40 The association remained even after adjusting for patient age.…”

Section: Pathogenesis and Pathophysiologymentioning

confidence: 96%

“…The degree of iris hypoplasia varies significantly between patients with iris tissue only observed by gonioscopy or optical coherence tomography (OCT) of the anterior segment in some. 83,114 In others, only slight hypoplasia is visible by slit lamp examination. This was seen as a bright gray and pale blue iris with a slightly decentered pupil in a patient initially considered to have a normal iris.126…”

Section: Iris Hypoplasiamentioning

confidence: 99%

Congenital aniridia – A comprehensive review of clinical features and therapeutic approaches

Landsend

Lagali

Utheim

2021

Survey of Ophthalmology

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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“…First described as "congenital irideremia" in the 19th century, congenital aniridia is a rare (1:60.000 to 1:90.000) pan-ocular disease that can be differentiated in 2 major categories depending on the presence of a PAX-6-Gene mutation [1,2,3,4]. Among those with a mutation of the PAX-6-Gene, frequent mutations involve point mutations and deletions.…”

Section: Introductionmentioning

confidence: 99%

An Attempt to Optimize the Outcome of Penetrating Keratoplasty in Congenital Aniridia-Associated Keratopathy (AAK).

Farah

Fries

Latta

et al. 2021

Preprint

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Purpose To propose an optimized microsurgical and medical approach to reduce the risk of complications after penetrating keratoplasty (PKP) in patients with aniridia-associated keratopathy (AAK). Methods Retrospective observational case series of 25 PKP performed in 16 patients with AAK. Preoperative indications were endothelial decompensation and vascularised scars (68%) or graft failure (32%) due to limbal stem cell deficiency. The optimized approach included a combination of a small corneal graft size (around 7.0mm), interrupted 10-0-Nylon sutures, simultaneous AMT as a patch, large bandage contact lens, temporary lateral tarsorrhaphy, postoperative autologous serum eye drops, and systemic immunosuppression. Main outcome measures included: Visual acuity, transplant survival and complications encountered during follow-up of 107 weeks on average. Results A complete modified keratoplasty scheme was used in 10 of 25 PKP (group 1), while at least one of the modifications was missing in the other 15 PKP (group 2). After 8 weeks follow-up, the epithelium was closed in 23 eyes. Visual acuity improved in 19 eyes at 6 months follow-up, and remained stable in 6 eyes. None of the eyes showed a decrease in visual acuity. At the last post-operative follow-up, this visual improvement persisted in 14 eyes and graft survival rate after 156 weeks (3 years) was 69% in group 1 vs. 44% in group 2 (p = 0.39, logrank test). Secondary corneal neovascularisation (8%), scarring (4%), ulcer (4%) or graft rejection (8%) happened mostly in the second group which was missing at least one of the suggested modifications. Conclusions PKP in congenital aniridia must be considered as a high-risk keratoplasty. An optimized therapeutic approach seems to be promising in order to reduce the postoperative complication rate in these most difficult eyes.

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Early phenotypic features of aniridia-associated keratopathy and association with PAX6 coding mutations

Cited by 38 publications

References 48 publications

The Spectrum of PAX6 Mutations and Genotype-Phenotype Correlations in the Eye

The Spectrum of PAX6 Mutations and Genotype-Phenotype Correlations in the Eye

Congenital aniridia – A comprehensive review of clinical features and therapeutic approaches

An Attempt to Optimize the Outcome of Penetrating Keratoplasty in Congenital Aniridia-Associated Keratopathy (AAK).

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