V van Heyningen

..However, detailed examination of the different mechanisms that underlie non-Mendelian segregation provides insight into the types of interaction that regulate more complex disease genetics...

..Upstream regulators and a multitude of downstream targets of PAX6 have been identified, and its varied tissue-specific functions are emerging...

..Loss of the reticulocalbin gene could contribute to the early lethality of SeyH and SeyDey homozygotes...

..Thus, at least five different eye phenotypes are associated with changes in PAX6 expression. We provide evidence that not only reduced, but also increased levels of transcriptional regulators can cause developmental defects...

..Our results support the hypothesis that the under-representation of missense mutations is caused by ascertainment bias and suggest that a substantial burden of PAX6 -related disease remains to be uncovered...

..Components of this downstream regulatory region drive reporter expression in distinct partial PAX6 patterns, indicating that the functional PAX6 gene domain extends far beyond the transcription unit...

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..Our results suggest that Pax6 plays a strong role during hindbrain migration processes and at least part of its activity is mediated through regulation of the netrin receptor Unc5h3...

..SSCP analysis of individually amplified exons, with which nine of the 10 mutations were seen, was the most useful detection method for PAX6...

..We therefore propose that a variety of anterior segment anomalies may be associated with PAX6 mutations...

..We suggest that this missense mutation is responsible both for aniridia and ptosis, and possibly also for the observed cognitive dysfunction in this family...

..Six previously unreported aniridia mutations in PAX6 are also described....

..Position effects with cytogenetic rearrangements well outside the coding region have been implicated for four of the genes discussed: POU3F4, SOX9, PAX6, and GL13...

..In a gene with such extraordinarily high sequence conservation throughout evolution, there are presumed undiscovered missense mutations, these are hypothesized to exist in as-yet unidentified phenotypes...

..The mutation is a single nucleotide change which, although occurring within an exon, affects the splice junction consensus and results in skipping of that exon...

..These mutations highlight regions of the gene which are essential for normal PAX6 function. In addition, the frequency at which we have found PAX6 mutations suggests that lesions in PAX6 will account for most cases of aniridia...

..Mutations that reduce Pax6 dosage cause dominantly inherited eye malformations in man and mouse. Remarkably, it has now been found that Drosophila has a homologue of Pax6, which also plays a key role in eye development...

..Here we report the analysis of three independent Sey alleles and show that indeed this gene is mutated and that the mutations would predictably interrupt gene function...

..These interactions also help us understand why there is significant phenotypic overlap between mutations at these three loci...

..A wider role in mesodermal differentiation is suggested by expression in some paraxial and lateral mesoderm derivatives...

..We propose that WT1 plays roles in posttranscriptional processing of RNA as well as in transcription...

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..1-10q24.3. The endogenous role of this enzyme appears to be in steroid oxidations. This cytochrome P-450 family does not correspond to any of the hepatic cytochrome P-450 gene families previously mapped in humans...

..Our results suggest that the large-scale genomic context of the breakpoint has prognostic utility and that the pathological mechanism of mapping to an R-band cannot be accounted for by direct gene inactivation...

..The detection of one nonsense point mutation and one missense WT1 gene point mutation adds to the accumulating evidence implicating this gene in a proportion of Wilms tumor patients...

..OMP is thus a candidate gene for both congenital deafness defects...

..Mutations in Pax-6 have been described previously in Small eye, the proposed mouse model for aniridia. We present new phenotypic evidence for the validity of this mouse model...

..This localization and the results of immunoprecipitation experiments suggest that the CD59 gene could encode the MIC11 antigen; alternatively this region of 11p13 may contain a cluster of genes encoding cell surface molecules...

..Cacy is shown to be within 8 kb of Capl in the mouse genome...

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..The concordance between expression and pathology, map location, structure, and predicted function argues that the cDNA corresponds to the AN gene...

..2. Pax6 establishes distinct ventral progenitor cell populations and controls the identity of motor neurons and ventral interneurons, mediating graded Shh signaling in the ventral spinal cord and hindbrain...

..On the basis of map position and expression pattern, EYA4 is a candidate for oculo-dento-digital (ODD) syndrome, but no EYA4 mutations were found in a panel of ODD patients...

..No pathogenic mutations were identified in the OFCD cases. A single PAX6 homeodomain missense mutation was identified in a subject with partial aniridia that had been initially misclassified as coloboma...