Fig. 1

a-d Genetic studies of the presented case against reported patients with pure distal 6p duplication. a Conventional GTG-banding performed at 550 band level showing additional genetic material at chromosome 6p (arrow). b Array CGH analysis. Above chromosome 6 ideogram log2 ratio of patient’s probes are plotted as a function of chromosomal position. Below the chromosome ideogram, mapping of breakpoints of other reported cases is shown. Of these, seven resulted from an insertion of the duplicated 6p fragment on another chromosome and five, including the present case, represent explicitly “pure” 6p duplications resulting from an intrachromosomal rearrangement. Note that for six cases – indicated with black asterisks - determination of the duplicated region was performed on cytogenetic level only, therefore the location of their breakpoints is only approximate. Chromosomal coordinates are presented according to NCBI36/hg18 assembly. The analysis was performed using Human CGH 3x720K Whole-Genome Tiling v3.0 Array (NimbleGen, Roche), scanned with MS200 Microarray Scanner (NimbleGen, Roche) and analyzed using Nexus Copy Number Software 7.1 (BioDiscovery). c Quantitative real-time PCR (qPCR) validation of array CGH. Dosage of the three genes localized in region of rearrangement: EXOC2, MAK and DCD2 (their loci indicated by arrows) relative to two reference genes: GPR15 (3q11.2) and ERMP1 (9p24.1) and normalized to reference DNA. Patient and her parents DNA were analyzed against a reference control DNA. All samples were run in triplicate. The diploid (two copies of a gene) samples have the normalized ratio = 1 (gray-colored band); whereas the normalized ratio of 1.5 and 0.5 refers to triploid and monoploid samples respectively. d FISH FISH analysis was performed using standard procedures with the bacterial artificial chromosome (BAC) clones specific for the aberration’s regions. The chromosome 6 breakpoints were mapped to 6p25.2 with BAC clone RP11-299 J5 (green signal) and to 6p22.1 with BAC clone RP11-121B12 (red signal). Left interphase; middle and right – metaphase