Partial monosomy 7q34-qter and 21pter-q22.13 due to cryptic unbalanced translocation t(7;21) but not monosomy of the whole chromosome 21: a case report plus review of the literature

<p>Abstract</p> <p>Background</p> <p>Autosomal monosomies in human are generally suggested to be incompatible with life; however, there is quite a number of cytogenetic reports describing full monosomy of one chromosome 21 in live born children. Here, we report a cytogenetically similar case associated with congenital malformation including mental retardation, motor development delay, craniofacial dysmorphism and skeletal abnormalities.</p> <p>Results</p> <p>Initially, a full monosomy of chromosome 21 was suspected as only 45 chromosomes were present. However, molecular cytogenetics revealed a de novo unbalanced translocation with a der(7)t(7;21). It turned out that the translocated part of chromosome 21 produced GTG-banding patterns similar to original ones of chromosome 7. The final karyotype was described as 45,XX,der(7)t(7;21)(q34;q22.13),-21. As a meta analysis revealed that clusters of the olfactory receptor gene family (ORF) are located in these breakpoint regions, an involvement of OFR in the rearrangement formation is discussed here.</p> <p>Conclusion</p> <p>The described clinical phenotype is comparable to previously described cases with ring chromosome 21, and a number of cases with del(7)(q34). Thus, at least a certain percentage, if not all full monosomy of chromosome 21 in live-borns are cases of unbalanced translocations involving chromosome 21.</p

Aneuploidy and Confined Chromosomal Mosaicism in the Developing Human Brain

BACKGROUND: Understanding the mechanisms underlying generation of neuronal variability and complexity remains the central challenge for neuroscience. Structural variation in the neuronal genome is likely to be one important mechanism for neuronal diversity and brain diseases. Large-scale genomic variations due to loss or gain of whole chromosomes (aneuploidy) have been described in cells of the normal and diseased human brain, which are generated from neural stem cells during intrauterine period of life. However, the incidence of aneuploidy in the developing human brain and its impact on the brain development and function are obscure. METHODOLOGY/PRINCIPAL FINDINGS: To address genomic variation during development we surveyed aneuploidy/polyploidy in the human fetal tissues by advanced molecular-cytogenetic techniques at the single-cell level. Here we show that the human developing brain has mosaic nature, being composed of euploid and aneuploid neural cells. Studying over 600,000 neural cells, we have determined the average aneuploidy frequency as 1.25-1.45% per chromosome, with the overall percentage of aneuploidy tending to approach 30-35%. Furthermore, we found that mosaic aneuploidy can be exclusively confined to the brain. CONCLUSIONS/SIGNIFICANCE: Our data indicates aneuploidization to be an additional pathological mechanism for neuronal genome diversification. These findings highlight the involvement of aneuploidy in the human brain development and suggest an unexpected link between developmental chromosomal instability, intercellural/intertissular genome diversity and human brain diseases

The frequency of chromosome losses and gains in the fetal human tissues exhibiting chromosomal mosaicism confined to the fetal brain.

<p>Aneuploidy frequency involving chromosomes 1, 9, 15, 16, 17, 18, X and Y was determined by interphase mFISH, MCB and PRINS techniques. (A) demonstration of selective chromosome X and chromosome Y gains, (B) demonstration of selective chromosome 15 loss, (C) demonstration of selective chromosome X loss, and (D) demonstration of selective chromosome 18 loss.</p

Molecular cytogenetic analysis of aneuploidy in the fetal human brain.

<p><b>(A to C)</b>. Interphase FISH with chromosome-enumeration DNA probes: (A) two nuclei characterized by additional chromosomes Y and X and a normal nucleus; (B) a nucleus with monosomy of chromosome 15 and a normal nucleus; (C) a nucleus with monosomy of chromosome 18 and a normal nucleus. (D to G) interphase chromosome-specific MCB: nuclei with monosomy, disomy, trisomy and G-banding ideograms with MCB color-code labeling of a chromosome (from left to right), (D) - chromosome 9, (E) - chromosome 16, and (F) - chromosome 18. (G) interphase QFISH: (1) a nucleus with two signals for chromosomes 18 (relative intensities: 2058 and 1772 pixels), (2) a nucleus with one paired signal mimics monosomy of chromosome 18 (relative intensity: 4012 pixels), (3) a nucleus with two signals for chromosomes 15 (relative intensities: 1562 and 1622 pixels), (4) a nucleus with one signal showing monosomy of chromosome 15 (relative intensity: 1678 pixels).</p

Stochastic aneuploidy frequency (%) involving chromosome loss and gain and the average chromosome instability index (losses and gains summed per individual chromosome pair) in the human fetal brain

<p>Stochastic aneuploidy frequency (%) involving chromosome loss and gain and the average chromosome instability index (losses and gains summed per individual chromosome pair) in the human fetal brain</p

Comparison of aneuploidy frequency in the fetal brain cells and chorionic villi cells detected by interphase mFISH analysis (12 fetuses analyzed).

<p>Eight arbitrary selected chromosomes (chromosomes 1, 9, 15, 16, 17, 18, X and Y) were analyzed for each fetus. No less than 5000 cells were scored for each chromosome for the brain tissue and 1000 cells for chorionic tissue.</p