Table 1.
Patients with isolated or syndromic aniridia carrying chromosomal deletions in 11p13.
Fig 1.
Identification of intragenic PAX6 deletion in patients with isolated aniridia.
Targeted array-based comparative genomic hybridization (aCGH) analysis identified two deletions involving partial PAX6 deletions in two patients. Colored bars represent the genomic positions of the deletions. Schematic representation of the complete intron-exon structure of PAX6 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 versus 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 PAX6 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 PAX6 gene found in patient ANIRIDIA-039 (chr11:31,820,789–31,824,052).
Fig 2.
Identification of 3’ regulatory deletions of PAX6 in patients with isolated aniridia.
Targeted array-based comparative genomic hybridization (aCGH) analysis identified deletions involving telomeric deletions to PAX6 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 PAX6 regulatory regions located in intronic positions of ELP4, as reviewed by Bathia, et al, 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 PAX6 deletions are shown. The patient versus 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).
Fig 3.
Identification of chromosomal rearrangements in WAGR locus in syndromic and non-syndromic patients with aniridia.
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 PAX6 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 PAX6, 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 PAX6 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.