Genetics and epidemiology of aniridia: Updated guidelines for genetic study

Blanco‐Kelly, Fiona; Tarilonte, M.; Villamar, Manuela; Damián, Alejandra; Tamayo, Alejandra; Moreno-Pelayo, Miguel A.; Ayuso, Carmen; Cortón, Marta

doi:10.1016/j.oftale.2021.02.002

Cited by 10 publications

(6 citation statements)

References 42 publications

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“…In such cases, the PAX6 protein is truncated and likely results in loss of function, or the mutated mRNA transcript is degraded through nonsense-mediated decay preventing translation. [ 8 26 27 ] Because of the dosage sensitivity of PAX6, the reduction of protein levels induces haploinsufficiency. [ 8 ] A recent longitudinal study of 86 aniridia patients in the UK supported the previous findings that missense variants are associated with milder phenotypes (milder grades of foveal and iris hypoplasia, cataracts, and aniridia-related keratopathy), with the exception to those that disrupt PAX6 DNA-binding activity, such as the c.372C > A, p.(Asn124Lys) variant, which gives rise to a non-aniridia phenotype of microphthalmia and coloboma.…”

Section: Pax6 and Aniridiamentioning

confidence: 99%

PAX6 disease models for aniridia

Abdolkarimi

Cunha²,

Lahne

et al. 2022

Indian Journal of Ophthalmology

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Aniridia is a pan-ocular genetic developmental eye disorder characterized by complete or partial iris and foveal hypoplasia, for which there is no treatment currently. Progressive sight loss can arise from cataracts, glaucoma, and aniridia-related keratopathy, which can be managed conservatively or through surgical intervention. The vast majority of patients harbor heterozygous mutations involving the PAX6 gene, which is considered the master transcription factor of early eye development. Over the past decades, several disease models have been investigated to gain a better understanding of the molecular pathophysiology, including several mouse and zebrafish strains and, more recently, human-induced pluripotent stem cells (hiPSCs) derived from aniridia patients. The latter provides a more faithful cellular system to study early human eye development. This review outlines the main aniridia-related animal and cellular models used to study aniridia and highlights the key discoveries that are bringing us closer to a therapy for patients.

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Section: Pax6 and Aniridiamentioning

confidence: 99%

PAX6 disease models for aniridia

Abdolkarimi

Cunha²,

Lahne

et al. 2022

Indian Journal of Ophthalmology

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“…Our case study aims to provide a comprehensive report of the PAX6 isoforms in a healthy individual. Mutations in PAX6 are responsible for nearly 100% of the cases of congenital aniridia, a rare developmental disease characterized by abnormalities in the iris and fovea (Blanco-Kelly et al 2021 )⁠. Two hotspot exons, EX5 and EX6, are prone to suffer naturally alternative splicing, resulting in a mixture of different splicing isoforms (Tarilonte et al 2022 )⁠.…”

Section: Discussionmentioning

confidence: 99%

VIsoQLR: an interactive tool for the detection, quantification and fine-tuning of isoforms in selected genes using long-read sequencing

et al. 2023

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DNA variants altering the pre-mRNA splicing process represent an underestimated cause of human genetic diseases. Their association with disease traits should be confirmed using functional assays from patient cell lines or alternative models to detect aberrant mRNAs. Long-read sequencing is a suitable technique to identify and quantify mRNA isoforms. Available isoform detection and/or quantification tools are generally designed for the whole transcriptome analysis. However experiments focusing on genes of interest need more precise data fine-tuning and visualization tools.Here we describe VIsoQLR, an interactive analyzer, viewer and editor for the semi-automated identification and quantification of known and novel isoforms using long-read sequencing data. VIsoQLR is tailored to thoroughly analyze mRNA expression in splicing assays of selected genes. Our tool takes sequences aligned to a reference, and for each gene, it defines consensus splice sites and quantifies isoforms. VIsoQLR introduces features to edit the splice sites through dynamic and interactive graphics and tables, allowing accurate manual curation. Known isoforms detected by other methods can also be imported as references for comparison. A benchmark against two other popular transcriptome-based tools shows VIsoQLR accurate performance on both detection and quantification of isoforms. Here, we present VIsoQLR principles and features and its applicability in a case study example using nanopore-based long-read sequencing. VIsoQLR is available at https://github.com/TBLabFJD/VIsoQLR.

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“…Однако они имеют генетически обусловленные различия. Аниридии встречаются с распространенностью 1 : 50 000-100 000 живорожденных и связаны с мутациями в гене PAX6, который управляет эмбриональным развитием нескольких тканей и органов, включая глаза, поджелудочную железу и ЦНС [9,10]. При врожденных аниридиях главной, но не единственной причиной слабовидения и нистагма является отсутствие радужной оболочки, хотя часто также встречается гипоплазия фовеа (центральной ямки сетчатки).…”

Section: обоснованиеunclassified

Levels of Neurospecific Peptides, Neurotransmitters and Neuroreceptor Markers in the Serum of Children with Various Sensory Disorders, Mild Cognitive Impairments and Other Neuropathology

et al. 2023

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Background. The role of recently discovered neurospecific peptides in the pathogenesis of acute and progressive neurologic disorders, their neuroprotective features, and possibilities to use them as markers for the course and prognosis of certain diseases have been actively studied in recent decades. However, neurospecific peptides are almost not studied in chronic residual diseases. In our study we measured the levels of neurospecific peptides and some other markers to achieve understanding of general neurophysiological trends in congenital and acquired chronic non-progressive brain pathology with reference to the selection of relevant groups — study objects. Objective. The aim of the study is to study patterns of neurospecific peptides, neurotransmitters and neuroreceptor markers distribution in the serum of children with various pathogenetic variants of chronic neuropathology. Methods. The study included children from 3 to 16 years old with different pathologies. The sample was divided into groups by pathology type: no sensory and neurological disorders, congenital sensory deficit due to mutation of genes expressed and not expressed in the brain, early acquired sensory deficit of multifactorial nature, congenital mild and severe organic disorders of central nervous system (CNS) in residual stage without baseline sensory deficit, acquired functional CNS disorders without baseline organic defect and sensory deficit. The following laboratory data (neurophysiological components) was studied: nerve growth factor, brain-derived neurotropic factor, neurotrophin-3, neurotrophin-4, neuregulin-1-beta-1, beta-secretase, sirtuin-1, synaptophysin, neuronal nitric oxide synthase, and anti-NR2 glutamate receptor antibodies. The parameters of cognitive activity, sense of vision, sense of smell, and acoustic sense were also evaluated. Results. The study included 274 participants. Neuropeptides and markers have shown a variable degree and range in the group spectrum of differences from normal levels. The most variable in the examined sample was NO-synthase, as well as levels of both neurotrophins, beta-secretase, and glutamate receptor marker. All visual deficits were associated with increased NO-synthase levels (p < 0.001). Neuroplasticity peptides (beta-secretase, neurotrophin-3 and 4) have been activated in all pathological conditions. Nerve growth factor and brain-derived neurotropic factor were specifically activated in mild organic CNS lesions (mild cognitive impairments), while neuregulin — in congenital genetically determined visual deficits. There was no specific activation of neuropeptides and NO-synthase level tended to decrease in cases of severe CNS lesions. Conclusion. The study results suggest that all types of early visual impairment are associated with increased physiological neuronal activity, and non-organic neurological functional disorders — mainly with increased physiological synaptic activity. General neuroplasticity processes were activated in all cases of visual deficits but more specific. However, more specific and well-studied processes were activated in mild organic CNS lesions, and neuroplasticity processes did not activate adequately in severe organic CNS lesions probably due to the limited neuronal and synaptic resources.

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Genetics and epidemiology of aniridia: Updated guidelines for genetic study

Cited by 10 publications

References 42 publications

PAX6 disease models for aniridia

PAX6 disease models for aniridia

VIsoQLR: an interactive tool for the detection, quantification and fine-tuning of isoforms in selected genes using long-read sequencing

Levels of Neurospecific Peptides, Neurotransmitters and Neuroreceptor Markers in the Serum of Children with Various Sensory Disorders, Mild Cognitive Impairments and Other Neuropathology

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