Figure 3

Chromosomal rearrangements upstream of SOX9 presumptively associated with SOX9 misregulation. Balanced and unbalanced rearrangements with breakpoints mapped upstream of SOX9, detected in patients with campomelic dysplasia (CD; blue), acampomelic campomelic dysplasia (ACD; red), Pierre Robin Sequence (PRS; green), minor or no skeletal defects (gray) and brachydactyly-anonychia (black) are shown. The centromeric limit of the two deletions represented by arrows extends beyond the region shown. SOX9 and other nearby genes are depicted. The breakpoints of balanced rearrangements are grouped into proximal, distal and PRS breakpoint clusters, according to their distance from SOX9; the herein described t(17;20) redefines the telomeric boundary of the distal cluster (see Table 1 for details). Disorders of sex development (DSD) are indicated: XY SDS (black circle symbol) and XX SDS (black triangle symbol). SOX9 regulatory elements E1 and E2[21], TESCO[22], and E3[10] are shown in the upper part of the figure (black oval symbol). The candidate region for the TESTIS-SPECIFIC ENHANCER[13], represented by the vertical bar, is spanned by all deletions and duplications detected in patients with DSD. (Based on UCSC Genome Bioinformatics, hg19).