A de novo nonsense mutation of <i>PAX6</i> gene in a patient with aniridia, ataxia, and mental retardation

Graziano, Claudio; D'Elia, Angela; Mazzanti, Laura; Moscano, Filomena; Guidi, Simonetta Guidelli; Scarano, Emanuela; Turchetti, Daniela; Franzoni, Emilio; Romeo, Giovanni; Damante, Giuseppe; Seri, Marco

doi:10.1002/ajmg.a.31808

Cited by 28 publications

(30 citation statements)

References 29 publications

(31 reference statements)

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“…In keeping with this, two previously cited PAX6 anti-termination mutations that resulted in translation into the 3′ untranslated region produced autism or autism spectrum phenotypes in addition to aniridia (Chao et al 2003;Heyman et al 1999). Also, a de novo nonsense mutation in exon 10, which falls within the 3′ end of the gene containing the PST transactivation domain, was recently found in an individual with aniridia and mental retardation (Graziano et al 2007). It was for this reason that the last exon of PAX6 was screened for mutations in our sample of 400 autism probands.…”

Section: Discussionmentioning

confidence: 68%

“…It is well known that PAX6 influences development of the nervous system and brain through regulation of proneural genes such as neurogenin 2 (Ngn2) and achaete-scute complex homolog-like 1 (Mash-1) (van Heyningen and Williamson 2002;Scardigli et al (2003). In human populations, recent studies have identified individuals with PAX6 mutations who present only with mental retardation and aniridia (Malandrini et al 2001;Ticho et al (2006;Graziano et al (2007). MRI studies of patients with aniridia and no obvious intellectual deficits have shown subtle brain abnormalities including a lack of the anterior commisure and pineal gland (Mitchell et al 2003).…”

Section: Introductionmentioning

confidence: 99%

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Pax6 3′ deletion results in aniridia, autism and mental retardation

et al. 2008

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The PAX6 gene is a transcription factor expressed early in development, predominantly in the eye, brain and gut. It is well known that mutations in PAX6 may result in aniridia, Peter's anomaly and kertatisis. Here, we present mutation analysis of a patient with aniridia, autism and mental retardation. We identified and characterized a 1.3 Mb deletion that disrupts PAX6 transcriptional activity and deletes additional genes expressed in the brain. Our findings provide continued evidence for the role of PAX6 in neural phenotypes associated with aniridia.

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Section: Discussionmentioning

confidence: 68%

Section: Introductionmentioning

confidence: 99%

Pax6 3′ deletion results in aniridia, autism and mental retardation

et al. 2008

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“…PAX6 intragenic mutations have been reported in two individuals with phenotypes overlapping Gillespie syndrome, but these cases probably have atypical aniridia. 41,42 The molecular basis of classical Gillespie syndrome is unidentified.…”

Section: Central Nervous Systemmentioning

confidence: 99%

Aniridia

Hingorani

Hanson²,

Heyningen³

2012

Eur J Hum Genet

206

224

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“…comm.). In some cases, cognitive impairment (Heyman et al 1999;Ticho et al 2006), mental retardation, and cerebellar ataxia (Graziano et al 2007) were reported. Structural and functional brain anomalies have also been observed (Sisodiya et al 2001;Mitchell et al 2003;Bamiou et al 2007).…”

mentioning

confidence: 99%

Discovery and assessment of conserved Pax6 target genes and enhancers

Coutinho¹,

Pavlou²,

Bhatia³

et al. 2011

Genome Res.

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The characterization of transcriptional networks (TNs) is essential for understanding complex biological phenomena such as development, disease, and evolution. In this study, we have designed and implemented a procedure that combines in silico target screens with zebrafish and mouse validation, in order to identify cis-elements and genes directly regulated by Pax6. We chose Pax6 as the paradigm because of its crucial roles in organogenesis and human disease. We identified over 600 putative Pax6 binding sites and more than 200 predicted direct target genes, conserved in evolution from zebrafish to human and to mouse. This was accomplished using hidden Markov models (HMMs) generated from experimentally validated Pax6 binding sites. A small sample of genes, expressed in the neural lineage, was chosen from the predictions for RNA in situ validation using zebrafish and mouse models. Validation of DNA binding to some predicted cis-elements was also carried out using chromatin immunoprecipitation (ChIP) and zebrafish reporter transgenic studies. The results show that this combined procedure is a highly efficient tool to investigate the architecture of TNs and constitutes a useful complementary resource to ChIP and expression data sets because of its inherent spatiotemporal independence. We have identified several novel direct targets, including some putative disease genes, among them Foxp2; these will allow further dissection of Pax6 function in development and disease.

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A de novo nonsense mutation of PAX6 gene in a patient with aniridia, ataxia, and mental retardation

Cited by 28 publications

References 29 publications

Pax6 3′ deletion results in aniridia, autism and mental retardation

Pax6 3′ deletion results in aniridia, autism and mental retardation

Aniridia

Discovery and assessment of conserved Pax6 target genes and enhancers

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