Molecular analysis of the PAX6 gene for aniridia and congenital cataracts in Tunisian families

Chograni, Manèl; Derouiche, Kaouther; Chaâbouni, M; Lariani, Imen; Bouhamed, Habiba Chaabouni

doi:10.1038/hgv.2014.8

Cited by 6 publications

(5 citation statements)

References 9 publications

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“…In this study, PAX6 was identified as the gene associated with microphthalmia, congenital cataracts, and foveal hypoplasia in family MA_2, which showed an extremely high intrafamiliar variability with regard to the clinical symptoms, affected ocular tissues, severity, and laterality. These findings are in accordance with previous reports in which variable phenotypes associated with PAX6 were described within the same family (Vincent et al 2004;Chograni et al 2014). The third gene mutation identified in our cohort, in RBP4, was found in a patient with microphthalmia and coloboma (pedigree MA_3), as has been reported in only three other families (Chou et al 2015).…”

Section: Discussionsupporting

confidence: 93%

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Panel‐based whole exome sequencing identifies novel mutations in microphthalmia and anophthalmia patients showing complex Mendelian inheritance patterns

Riera

Wert

Nieto

et al. 2017

Molec Gen & Gen Med

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BackgroundMicrophthalmia and anophthalmia (MA) are congenital eye abnormalities that show an extremely high clinical and genetic complexity. In this study, we evaluated the implementation of whole exome sequencing (WES) for the genetic analysis of MA patients. This approach was used to investigate three unrelated families in which previous single‐gene analyses failed to identify the molecular cause.MethodsA total of 47 genes previously associated with nonsyndromic MA were included in our panel. WES was performed in one affected patient from each family using the AmpliSeqTM Exome technology and the Ion ProtonTM platform.ResultsA novel heterozygous OTX2 missense mutation was identified in a patient showing bilateral anophthalmia who inherited the variant from a parent who was a carrier, but showed no sign of the condition. We also describe a new PAX6 missense variant in an autosomal‐dominant pedigree affected by mild bilateral microphthalmia showing high intrafamiliar variability, with germline mosaicism determined to be the most plausible molecular cause of the disease. Finally, a heterozygous missense mutation in RBP4 was found to be responsible in an isolated case of bilateral complex microphthalmia.ConclusionThis study highlights that panel‐based WES is a reliable and effective strategy for the genetic diagnosis of MA. Furthermore, using this technique, the mutational spectrum of these diseases was broadened, with novel variants identified in each of the OTX2,PAX6, and RBP4 genes. Moreover, we report new cases of reduced penetrance, mosaicism, and variable phenotypic expressivity associated with MA, further demonstrating the heterogeneity of such disorders.

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Section: Discussionsupporting

confidence: 93%

“…; Chograni et al. ). The third gene mutation identified in our cohort, in RBP4 , was found in a patient with microphthalmia and coloboma (pedigree MA_3), as has been reported in only three other families (Chou et al.…”

Section: Discussionmentioning

confidence: 98%

Panel‐based whole exome sequencing identifies novel mutations in microphthalmia and anophthalmia patients showing complex Mendelian inheritance patterns

Riera

Wert

Nieto

et al. 2017

Molec Gen & Gen Med

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“…NCCs give rise, for instance, to the corneal endothelium, the corneal stroma and the stroma of the ciliary body and the iris. Not surprisingly, NCC deficiencies lead to corneal diseases, such as anterior segment dysgenesis (ASD), 26,27 as seen with Axenfeld‐Rieger syndrome, 28,29 Peters anomaly, 30 Aniridia 31 and Nail Patella syndrome 32 . The major clinicopathological characteristics of ASD include corneal epithelial dystrophy, disorganized corneal stroma, sclerocornea, corneal opacities and corneal vascularization 27 .…”

Section: Introductionmentioning

confidence: 99%

KIT ligand produced by limbal niche cells under control of SOX10 maintains limbal epithelial stem cell survival by activating the KIT/AKT signalling pathway

Wang

Lai

et al. 2020

J Cellular Molecular Medi

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Limbal epithelial stem cells (LESCs) play critical roles in regulating homeostasis of the corneal epithelium. Loss of LESCs leads to severe corneal disease, called limbal epithelial stem cell deficiency (LSCD), which is associated with corneal neovascularization, stromal scarring and impaired visual acuity. 1 LESCs transplantation represents a feasible therapeutic approach to LSCD, but according to statistical analysis of clinical trials, this approach has nevertheless failed to improve vision in 26.7%-60% of LSCD patients. These therapeutic failures may be due to the limited life span of LESCs. 2-12 Evidently, a detailed analysis of the molecular mechanisms of LESC maintenance is of paramount importance to design approaches to enhance the success of therapeutic transplantation, or better still, to be able to interfere with LESC loss early in the disease process. 13 The maintenance of adult stem cells relies on stem cell niches whose microenvironment contains an extracellular matrix and cells that provide autocrine and paracrine signals necessary for the proper function of the respective stem cells. There is increasing evidence that one of the major type of niche cells supporting

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“…Another form of ASD is aniridia, which involves absence of the iris, and studies in patient populations with aniridia have revealed several mutations within the paired box protein 6 ( Pax6 ) gene that were associated with this phenotype (Chograni, Derouiche, Chaabouni, Lariani, & Bouhamed, ). PAX6 is normally expressed in the surface ectoderm and neuroectoderm‐derived tissue, such as the retina.…”

Section: Rare Human Ocular Disorders and The Neural Crestmentioning

confidence: 99%

Relationship between neural crest cell specification and rare ocular diseases

Akula

Park

West‐Mays

2018

J of Neuroscience Research

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Development of the eye is closely associated with neural crest cell migration and specification. Eye development is extremely complex, as it requires the working of a combination of local factors, receptors, inductors, and signaling interactions between tissues such as the optic cup and periocular mesenchyme (POM). The POM is comprised of neural crest-derived mesenchymal progenitor cells that give rise to numerous important ocular structures including those tissues that form the optic cup and anterior segment of the eye. A number of genes are involved in the migration and specification of the POM such as PITX2, PITX3, FOXC1, FOXE3, PAX6, LMX1B, GPR48, TFAP2A, and TFAP2B. In this review, we will discuss the relevance of these genes in the development of the POM and how mutations and defects result in rare ocular diseases.

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Molecular analysis of the PAX6 gene for aniridia and congenital cataracts in Tunisian families

Cited by 6 publications

References 9 publications

Panel‐based whole exome sequencing identifies novel mutations in microphthalmia and anophthalmia patients showing complex Mendelian inheritance patterns

Panel‐based whole exome sequencing identifies novel mutations in microphthalmia and anophthalmia patients showing complex Mendelian inheritance patterns

KIT ligand produced by limbal niche cells under control of SOX10 maintains limbal epithelial stem cell survival by activating the KIT/AKT signalling pathway

Relationship between neural crest cell specification and rare ocular diseases

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