Fig. 2

Identification of a reciprocal translocation t(6;11) affecting the PAX6 downstream regulatory region in patient ANI-2. a–b. Representation of long-reads, breakpoints, and genomic elements involved in the paracentric inversion using IGV and Ribbon visualizers from vcf and BAM files. LRS showed evidence of an interchromosomal translocation involving alpha-satellite DNA sequences from the centromeric region of chromosome 6 (6p11.1) and their mate split reads laying on chromosome 11 (11p13) in intron 9 of the ELP4 gene. The breakpoint on 11p13 disrupts the DNase I hypersensitive site 2 (HS2) enhancer within the downstream regulatory region (DRR) of PAX6. This chromosomal break is taking apart PAX6 from its critical 18 Kb minimal regulatory region defined by Plaisancie et al., 2018 [10]. c–d. Karyotyping and FISH analysis showed the presence of a t(6;11) reciprocal translocation. Schematic representation of the FISH assay designed to visualize the breakpoints. The centromeric CEP6-D6Z1 and PAX6 probes are labeled in cyan blue and red, respectively. FISH images showed specific signals for PAX6 and CEP6-D6Z1 alpha-satellite sequences on derivative chromosome 11, der (11). A signal for CEP6-D6Z1 was also observed on derivative chromosome 6, der(6), confirming breakpoint involvement at the centromeric level