A Review of the Clinical and Genetic Aspects of Aniridia

Lee, Hyunjoo J; Colby, Kathryn

doi:10.3109/08820538.2013.825293

Cited by 69 publications

(59 citation statements)

References 34 publications

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“…The PAX6 gene encodes a transcription factor critical for normal embryonic development. The PAX6 protein is expressed in the developing eye, multiple brain regions, olfactory bulb, neural tube, gut, and pancreas [10]. In humans, insufficient PAX6 protein expression results in severe congenital defects of the eye [11].…”

Section: Embryological Origins Of the Ocular Surface Epitheliamentioning

confidence: 99%

An Update on Ocular Surface Epithelial Stem Cells: Cornea and Conjunctiva

Ramos

Scott

Ahmad

2015

Stem Cells International

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The human ocular surface (front surface of the eye) is formed by two different types of epithelia: the corneal epithelium centrally and the conjunctival epithelium that surrounds this. These two epithelia are maintained by different stem cell populations (limbal stem cells for the corneal epithelium and the conjunctival epithelial stem cells). In this review, we provide an update on our understanding of these epithelia and their stem cells systems, including embryology, new markers, and controversy around the location of these stem cells. We also provide an update on the translation of this understanding into clinical applications for the treatment of debilitating ocular surface diseases.

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Section: Embryological Origins Of the Ocular Surface Epitheliamentioning

confidence: 99%

An Update on Ocular Surface Epithelial Stem Cells: Cornea and Conjunctiva

Ramos

Scott

Ahmad

2015

Stem Cells International

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“…Heterozygous mutations in the PAX6 gene, which result in the production of a truncated, non-functional protein (9), cause abnormal iris formation (aniridia) and impaired glucose tolerance (10). Correspondingly, PAX6 binding domains are found in the promoter regions of several key β cell genes (11), and islets derived from a human pedigree harboring an inactivating missense PAX6 mutation are deficient in proinsulin processing enzymes (PCSK1/3) (12).…”

Section: Introductionmentioning

confidence: 99%

The transcription factor Pax6 is required for pancreatic β cell identity, glucose-regulated ATP synthesis, and Ca2+ dynamics in adult mice

Mitchell

Nguyen-Tu

Chabosseau

et al. 2017

Journal of Biological Chemistry

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Heterozygous mutations in the human paired box gene PAX6 lead to impaired glucose tolerance. Although embryonic deletion of the Pax6 gene in mice leads to loss of most pancreatic islet cell types, the functional consequences of Pax6 loss in adults are poorly defined. Here we developed a mouse line in which Pax6 was selectively inactivated in β cells by crossing animals with floxed Pax6 alleles to mice expressing the inducible Pdx1CreERT transgene. Pax6 deficiency, achieved by tamoxifen injection, caused progressive hyperglycemia. Although β cell mass was preserved 8 days post-injection, total insulin content and insulin:chromogranin A immunoreactivity were reduced by ∼60%, and glucose-stimulated insulin secretion was eliminated. RNA sequencing and quantitative real-time PCR analyses revealed that, although the expression of key β cell genes, including Ins2, Slc30a8, MafA, Slc2a2, G6pc2, and Glp1r, was reduced after Pax6 deletion, that of several genes that are usually selectively repressed (“disallowed”) in β cells, including Slc16a1, was increased. Assessed in intact islets, glucose-induced ATP:ADP increases were significantly reduced (p < 0.05) in βPax6KO versus control β cells, and the former displayed attenuated increases in cytosolic Ca2+. Unexpectedly, glucose-induced increases in intercellular connectivity were enhanced after Pax6 deletion, consistent with increases in the expression of the glucose sensor glucokinase, but decreases in that of two transcription factors usually expressed in fully differentiated β-cells, Pdx1 and Nkx6.1, were observed in islet “hub” cells. These results indicate that Pax6 is required for the functional identity of adult β cells. Furthermore, deficiencies in β cell glucose sensing are likely to contribute to defective insulin secretion in human carriers of PAX6 mutations.

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“…Among the mutations, there are 33.3% nonsense and 17.7% missense mutations, respectively ( PAX6 mutation database, http://lsdb.hgu.mrc.ac.uk/home.php?select_db=PAX6). There is no definite correlation between the clinical phenotype and the location of PAX6 mutations9). However, in Korean patients with congenital aniridia, PAX6 mutations have been reported more frequently in exons 7 and 8101112).…”

Section: Discussionmentioning

confidence: 99%

A nonsensePAX6mutation in a family with congenital aniridia

Han

Lee

et al. 2016

Korean J Pediatr

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Congenital aniridia is a rare ocular malformation that presents with severe hypoplasia of the iris and various ocular manifestations. Most cases of congenital aniridia are known to be related to mutations in the paired box gene-6 (PAX6), which is an essential gene in eye development. Herein, we report a familial case of autosomal dominant congenital aniridia with four affected members in 3 consecutive generations and describe the detailed ophthalmologic findings for one of these members. As expected, mutational analysis revealed a nonsense mutation (p.Ser122*) in the PAX6 gene. Thus, our findings reiterate the importance of PAX6 mutations in congenital aniridia.

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A Review of the Clinical and Genetic Aspects of Aniridia

Cited by 69 publications

References 34 publications

An Update on Ocular Surface Epithelial Stem Cells: Cornea and Conjunctiva

An Update on Ocular Surface Epithelial Stem Cells: Cornea and Conjunctiva

The transcription factor Pax6 is required for pancreatic β cell identity, glucose-regulated ATP synthesis, and Ca2+ dynamics in adult mice

A nonsensePAX6mutation in a family with congenital aniridia

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