Phenotypic variation in a four-generation family with aniridia carrying a novel PAX6 mutation

Wang, Grace M.; Prasov, Lev; Richards, Julia E.; Bohnsack, Brenda L.

doi:10.1016/j.jaapos.2017.07.129

Cited by 3 publications

(2 citation statements)

References 38 publications

(60 reference statements)

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“…Notably, mutations in Pax6 are more typically associated with aniridia, a panocular congenital disease characterized by foveal hypoplasia, optic nerve hypoplasia, limbal stem cell deficiency, and varying degrees of iris hypoplasia (reviewed in Lim et al, 2017;Sannan et al, 2017;Syrimis et al, 2018;Wawrocka and Krawczynski, 2018;Lima Cunha et al, 2019;Lee et al, 2020;Tripathy and Salini, 2020). However, phenotypic variation of the same Pax6 gene mutation has shown both aniridia and PA within one family (Wang et al, 2018), and PA has been associated with aniridia in more than 10% of cases (Dolezal et al, 2019).…”

Section: Peters Anomaly (Omim 604229)mentioning

confidence: 99%

The Ocular Neural Crest: Specification, Migration, and Then What?

Williams

Bohnsack

2020

Front. Cell Dev. Biol.

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During vertebrate embryonic development, a population of dorsal neural tube-derived stem cells, termed the neural crest (NC), undergo a series of morphogenetic changes and extensive migration to become a diverse array of cell types. Around the developing eye, this multipotent ocular NC cell population, called the periocular mesenchyme (POM), comprises migratory mesenchymal cells that eventually give rise to many of the elements in the anterior of the eye, such as the cornea, sclera, trabecular meshwork, and iris. Molecular cell biology and genetic analyses of congenital eye diseases have provided important information on the regulation of NC contributions to this area of the eye. Nevertheless, a complete understanding of the NC as a contributor to ocular development remains elusive. In addition, positional information during ocular NC migration and the molecular pathways that regulate end tissue differentiation have yet to be fully elucidated. Further, the clinical challenges of ocular diseases, such as Axenfeld-Rieger syndrome (ARS), Peters anomaly (PA) and primary congenital glaucoma (PCG), strongly suggest the need for better treatments. While several aspects of NC evolution have recently been reviewed, this discussion will consolidate the most recent current knowledge on the specification, migration, and contributions of the NC to ocular development, highlighting the anterior segment and the knowledge obtained from the clinical manifestations of its associated diseases. Ultimately, this knowledge can inform translational discoveries with potential for sorely needed regenerative therapies.

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Section: Peters Anomaly (Omim 604229)mentioning

confidence: 99%

The Ocular Neural Crest: Specification, Migration, and Then What?

Williams

Bohnsack

2020

Front. Cell Dev. Biol.

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“…A portion of this manuscript was presented at the 2017 Annual Meeting of the American Association of Pediatric Ophthalmology and Strabismus and published with the meeting abstracts in J AAPOS [ 62 ]. The authors alone are responsible for the content and writing of this article.…”

Section: Disclosurementioning

confidence: 99%

Phenotypic Variation in a Four-Generation Family with Aniridia Carrying a NovelPAX6Mutation

Wang

Prasov

Al-Hasani

et al. 2018

Journal of Ophthalmology

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Aniridia is a congenital disease that affects almost all eye structures and is primarily caused by loss-of-function mutations in the PAX6 gene. The degree of vision loss in aniridia varies and is dependent on the extent of foveal, iris, and optic nerve hypoplasia and the presence of glaucoma, cataracts, and corneal opacification. Here, we describe a 4-generation family in which 7 individuals across 2 generations carry a novel disease-causing frameshift mutation (NM_000280.4(PAX6):c.565TC>T) in PAX6. This mutation results in an early stop codon in exon 8, which is predicted to cause nonsense-mediated decay of the truncated mRNA and a functionally null PAX6 allele. Family members with aniridia showed differences in multiple eye phenotypes including iris and optic nerve hypoplasia, congenital and acquired corneal opacification, glaucoma, and strabismus. Visual acuity ranged from 20/100 to less than 20/800. Patients who required surgical intervention for glaucoma or corneal opacification had worse visual outcomes. Our results show that family members carrying a novel PAX6 frameshift mutation have variable expressivity, leading to different ocular comorbidities and visual outcomes.

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Genetic changes and testing associated with childhood glaucoma: A systematic review

Kumar,

Han,

Oatts

2024

PLoS ONE

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Many forms of childhood glaucoma have been associated with underlying genetic changes, and variants in many genes have been described. Currently, testing is variable as there are no widely accepted guidelines for testing. This systematic review aimed to summarize the literature describing genetic changes and testing practices in childhood glaucoma. This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic review and Meta-Analyses (PRISMA) 2020 guidelines and registered with Prospero (ID CRD42023400467). A comprehensive review of Pubmed, Embase, and Cochrane databases was performed from inception through March 2, 2023 using the search terms: (glaucoma) AND (pediatric OR childhood OR congenital OR child OR infant OR infantile) AND (gene OR genetic OR genotype OR locus OR genomic OR mutation OR variant OR test OR screen OR panel). Information was extracted regarding genetic variants including genotype-phenotype correlation. Risk of bias was assessed using the Newcastle-Ottawa Scale. Of 1,916 records screened, 196 studies met inclusion criteria and 53 genes were discussed. Among study populations, mean age±SD at glaucoma diagnosis was 8.94±9.54 years and 50.4% were male. The most common gene discussed was CYP1B1, evaluated in 109 (55.6%) studies. CYP1B1 variants were associated with region and population-specific prevalence ranging from 5% to 86% among those with primary congenital glaucoma. MYOC variants were discussed in 31 (15.8%) studies with prevalence up to 36% among patients with juvenile open angle glaucoma. FOXC1 variants were discussed in 25 (12.8%) studies, which demonstrated phenotypic severity dependent on degree of gene expression and type of mutation. Overall risk of bias was low; the most common domains of bias were selection and comparability. Numerous genes and genetic changes have been associated with childhood glaucoma. Understanding the most common genes as well as potential genotype-phenotype correlation has the potential to improve diagnostic and prognostic outcomes for children with glaucoma.

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Phenotypic variation in a four-generation family with aniridia carrying a novel PAX6 mutation

Cited by 3 publications

References 38 publications

The Ocular Neural Crest: Specification, Migration, and Then What?

The Ocular Neural Crest: Specification, Migration, and Then What?

Phenotypic Variation in a Four-Generation Family with Aniridia Carrying a NovelPAX6Mutation

Genetic changes and testing associated with childhood glaucoma: A systematic review

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