PMC4758088_01
Standard cytogenetic analysis of the patient. GTG-banded karyotype showing the presence of ring chromosome 18 (karyotype 46, XY, 18(r)). Red arrow points to the ring chromosome (mar: marker)
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Fig1
The standard cytogenetic analysis showed the presence of r(18) in proband's karyotype (46, XY, r(18)) (Fig. 1, Additional file 1) with the ring chromosome being revealed in all analyzed metaphase plates.
High-resolution molecular cytogenetic analysis of the patient. a, b Comparative genomic hybridization using Agilent 60 K microarray. a The chromosome 18 view; oligonucleotides with log2 ratio ~ -1 (red dots, red rectangles) indicate deleted regions; oligonucleotides with log2 ratio ~ +0.6 (blue dots, blue rectangle) indicate a duplicated region. The boundaries of terminal deletions, a duplication and an interstitial deletion (18q12.1) were defined with high resolution. b The enlarged 18q12.1 region with imported DGV and OMIM databases tracks and genes annotations. The data illustrate the presence of DTNA deletion. c, d Fluorescent in situ hybridization (FISH) on metaphases from cultured peripheral blood lymphocytes. FISH with probes to centromeric (aqua) and subtelomic (yellow) regions of chromosome 18 (ToTelVysion Probe Kit, Abbott/Vysis; the probes to subtelomeric regions of chromosomes 11 and 12 (p - green, q - red) are added in the hybridization mix by the manufacturer). Inserts show the enlarged view of the normal and the ring chromosome 18. The analysis confirmed the deletion of both terminal regions on r(18)
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Fig2
The deletion of both 18p and 18q terminal regions of r(18) was unambiguously confirmed by FISH with probes marking subtelomeric regions of chromosome 18 (Fig. 2c, d). Array-CGH analysis showed that 18p terminal deletion corresponded to the 18p11.32 cytoband (Fig. 2a) and spanned 305 kb (chr18: 132096-437282 bp, hg18 build). The 18q terminal deletion was assigned to the 18q22.3-q23 chromosomal region (Fig. 2a) with length about 7.5 Mb (chr18: 68533620-76083117 bp, hg18 build) that involves many annotated genes including OMIM morbid genes TSHZ1 and CTDP1. Apart from the terminal imbalances, an interstitial heterozygous deletion of 442 kb in size (chr18: 30327060-30769230 bp, hg18 build) was found on chromosome 18 (Fig. 2a, b).