Identification of chromosomal rearrangements in WAGR locus in syndromic and non-syndromic patients with aniridia.

<p>Targeted array-based comparative genomic hybridization (aCGH) analysis identified deletions of different sizes ranging from3.3 Kb to 13.4 Mb. The red bars show intragenic <i>PAX6</i> deletions in two patients with isolated aniridia, ANIRIDIA-039 (chr11:31,820,789–31,824,052) and ANIRIDIA-052 (chr11:31,760,458–31,823,847). The green bars show 3’ upstream deletions affecting 3' regulatory regions of <i>PAX6</i>, identified in three families with isolated aniridia: ANIRIDIA-008 (chr11:31,147,306–31,714,853), ANIRIDIA-021 (chr11:31,186,493–31,698,208) and ANIRIDIA-067 (chr11:31,083,877–31,704,548). Purple bars show large deletions affecting several contiguous genes, in two patients with WAGR (ANIRIDIA-020, chr11:29,750,813–32,752,091), and WAGRO (ANIRIDIA-070, chr11:21,586,131–33,168,232) syndromes. Genes delineating both syndromes are highlighted in red. The blue bar represents a novel gene contiguous deletion syndrome involving <i>PAX6</i> and 45 upstream genes in a syndromic patient with aniridia (ANIRIDIA-064, chr11:18,536,224–31,923,308). Genomic coordinates are shown in the x-axis and are based on the Human Genome Assembly hg19.</p

Identification of intragenic <i>PAX6</i> deletion in patients with isolated aniridia.

<p>Targeted array-based comparative genomic hybridization (aCGH) analysis identified two deletions involving partial <i>PAX6</i> deletions in two patients. Colored bars represent the genomic positions of the deletions. Schematic representation of the complete intron-exon structure of <i>PAX6</i> is shown. Exons are indicated by colored rectangles that are wider for the coding regions. CGH array data for both individuals is shown. The patient <i>versus</i> reference log2-ratio for the relative hybridization intensities of probes is plotted. Dots with log2-ratio around -1 indicate a heterozygous deletion (green dots), log2-ratio 0 indicates a normal pattern, and +0.6 indicates a heterozygous amplification (red dots). Shaded areas indicate deletions. Genomic coordinates are shown in the x-axis and are based on the Human Genome Assembly hg19. The red bar indicates a ~63 kb deletion encompassing from exon 5a to exon 13 of <i>PAX6</i> found in patient ANIRIDIA-052 (chr11:31,760,458–31,823,847). The grey bar represents a ~3.3 kb deletion encompassing from exon 5a to exon 7 of <i>PAX6</i> gene found in patient ANIRIDIA-039 (chr11:31,820,789–31,824,052).</p

Patients with isolated or syndromic aniridia carrying chromosomal deletions in 11p13.

<p>Patients with isolated or syndromic aniridia carrying chromosomal deletions in 11p13.</p

Identification of 3’ regulatory deletions of <i>PAX6</i> in patients with isolated aniridia.

<p>Targeted array-based comparative genomic hybridization (aCGH) analysis identified deletions involving telomeric deletions to <i>PAX6</i> in two patients ANIRIDIA-008 and ANIRIDIA-021. Patient ANIRIDIA-067 was used as positive control for validation purposes. The colored bars represent the genomic positions of the deletions. The red asterisks indicate a cluster of <i>PAX6</i> regulatory regions located in intronic positions of <i>ELP4</i>, as reviewed by Bathia, <i>et al</i>, 2013. Exons are indicated by colored rectangles that are wider for the coding regions. CGH array data for the two patients with previously unknown 3' telomeric <i>PAX6</i> deletions are shown. The patient <i>versus</i> reference log2-ratio for the relative hybridization intensities of probes is plotted. Dots with log2-ratio around -1 indicate a heterozygous deletion (green dots), log2-ratio 0 indicates a normal pattern and +0.6 indicates a heterozygous amplification (red dots). Shaded areas indicate deletions. Genomic coordinates are shown in the x-axis and are based on the Human Genome Assembly hg19. The grey bar indicates a ~567 kb deletion in patient ANIRIDIA-008 (chr11:31,147,306–31,714,853). The orange bar indicates a ~511 kb deletion in patient ANIRIDIA-021 (chr11:31,186,493–31,698,208).</p