Human Ring Chromosomes - New Insights for their Clinical Significance.

Twenty-nine as yet unreported ring chromosomes were characterized in detail by cytogenetic and molecular techniques. For FISH (fluorescence in situ hybridization) previously published high resolution approaches such as multicolor banding (MCB), subcentromere-specific multi-color-FISH (cenM-FISH) and two to three-color-FISH applying locus-specific probes were used. Overall, ring chromosome derived from chromosomes 4 (one case), 10 (one case), 13 (five cases), 14, (three cases), 18 (two cases), 21 (eight cases), 22 (three cases), X (five cases) and Y (one case) were studied.

A new multicolor fluorescence in situ hybridization probe set directed against human heterochromatin: HCM-FISH.

A new multicolor fluorescence in situ hybridization (mFISH) probe set is presented, and its possible applications are highlighted in 25 clinical cases. The so-called heterochromatin-M-FISH (HCM-FISH) probe set enables a one-step characterization of the large heterochromatic regions within the human genome. HCM-FISH closes a gap in the now available mFISH probe sets, as those do not normally cover the acrocentric short arms; the large pericentric regions of chromosomes 1, 9, and 16; as well as the band Yq12.

Biomarkers for genome instability in some genetic disorders: a pilot study.

Context: The study of genome integrity in some genetic disorders has diagnostic and prognostic importance because of the evident relationship between genome instability and both DNA repair deficiencies and cancer predisposition.

Objective: The objective was to compare the chromosomal and DNA damage responses in lymphocytes from patients with Nijmegen breakage syndrome (NBS), Fanconi anemia (FA) and Williams-Beuren syndrome (WBS) to find additional biomarkers of genome instability.

Methods: The cytogenetic approaches were combined with the alkaline Comet assay to estimate genome integrity in cultured or freshly isolated and H(2)O(2)-treated lymphocytes.

Five novel locations of Neocentromeres in human: 18q22.1, Xq27.1∼27.2, Acro p13, Acro p12, and heterochromatin of unknown origin.

Since the first report in 1993, an ectopic centromere, i.e. neocentromere formation, has been reported in more than 100 small supernumerary marker chromosomes (sSMC), in 7 instances of centromere repositioning, and in about a dozen cases with more complex chromosomal rearrangements.

Chromosomal instability at the 7q11.23 region impacts on DNA-damage response in lymphocytes from Williams-Beuren syndrome patients.

Williams-Beuren syndrome (WBS) is the chromosomal disorder arising from a hemizygous microdeletion at 7q11.23. The present study was focused on a comparative investigation of genomic integrity in WBS patients by use of cytogenetic methods and the alkaline comet assay.

Two siblings with immunodeficiency, facial abnormalities and chromosomal instability without mutation in DNMT3B gene but liability towards malignancy; a new chromatin disorder delineation?

Background: ICF syndrome (standing for Immunodeficiency, Centromere instability and Facial anomalies syndrome) is a very rare autosomal recessive immune disorder caused by mutations of the gene de novo DNA-methyltransferase 3B (DNMT3B). However, in the literature similar clinical cases without such mutations are reported, as well.

Results: We report on a family in which the unrelated spouses had two female siblings sharing similar phenotypic features resembling ICF-syndrome, i.

Molecular cytogenetic characterization of two cases with de novo small mosaic supernumerary marker chromosomes derived from chromosome 16: towards a genotype/phenotype correlation.

Small supernumerary marker chromosomes (sSMC) derived from chromosome 16 are rare and, so far, it is not yet clear which regions of chromosome 16 are critical and have clinical consequences. We have characterized two cases with a ring-shaped sSMC derived from chromosome 16. In case A the sSMC was encountered prenatally and was characterized using centromeric fluorescence in situ hybridization (FISH) probes, subcentromere-specific multicolor FISH (subcenM-FISH), reverse FISH and array-CGH, using a full-tiling BAC array specific for chromosome 16.

Paternally derived der(7)t(Y;7)(p11.1 approximately 11.2;p22.3)dn in a mosaic case with Turner syndrome.

An unusual mosaic karyotype was detected in a 6-year-old female patient with clinical diagnosis of Turner syndrome (TS). Cytogenetic and molecular cytogenetic studies revealed besides a cell line with 45,X a second cell line where the short arm of the Y-chromosome was translocated onto the short arm of a chromosome 7; karyotype: 45,X,der(7)t(Y;7)(p11.1 approximately 11.

Thirty-two new cases with small supernumerary marker chromosomes detected in connection with fertility problems: detailed molecular cytogenetic characterization and review of the literature.

Thirty-two patients with fertility problems were identified as carriers of small supernumerary marker chromosomes (sSMC). Molecular cytogenetic techniques were used to characterize their chromosomal origin. Together with the other cases available in the literature 111 sSMC cases have now been detected in connection with fertility problems in otherwise clinically healthy persons and characterized for their genetic content.

Small supernumerary marker chromosomes (sSMC) in patients with a 45,X/46,X,+mar karyotype - 17 new cases and a review of the literature.

Small supernumerary marker chromosomes (sSMC) can appear in a numerically normal 'basic karyotype', but also in a numerically abnormal one like a Turner syndrome karyotype (= sSMC(T)). Here we present 17 new cases with such a mos 45,X/46,X,+mar karyotype. Moreover we reviewed all 512 cytogenetically similar cases available from the literature and supply for the first time data on occurrence, shapes and subgroups of this rare cytogenetic entity.

Forty-eight new cases with infertility due to balanced chromosomal rearrangements: detailed molecular cytogenetic analysis of the 90 involved breakpoints.

A molecular cytogenetic study was performed on 48 infertile patients who were identified as carriers of balanced translocations (40 cases), inversions (6 cases) or insertions (2 cases) by means of banding cytogenetics. Cases with a Robertsonian translocation or pericentric inversion 2 or 9 were not included. In summary, 100 break-events occurred in these patients, and 90 different chromosomal regions were involved.

Duplications of proximal 16q flanked by heterochromatin are not euchromatic variants and show no evidence of heterochromatic position effect.

Extra euchromatic material was found within the major heterochromatic block of chromosome 16 (16qh) in one de novo case and seven members of two families. In contrast to the euchromatic variants of chromosome 9 (9qh), which are derived from pericentromeric euchromatin, molecular cytogenetics confirmed that these duplications were of 16q11.2-->q12.

Small supernumerary marker chromosomes--progress towards a genotype-phenotype correlation.

Small supernumerary marker chromosomes (sSMC) are still a major problem in clinical cytogenetics as they are too small to be characterized for their chromosomal origin by traditional banding techniques, but require molecular cytogenetic techniques for their identification. Apart from the correlation of about one third of the sSMC cases with a specific clinical picture, i.e.

Tetrasomy 12pter-12p13.31 in a girl with partial Pallister-Killian syndrome phenotype.

A dysmorphic patient was shown to carry a small supernumerary marker chromosome. Multicolor, centromere-multicolor and regular FISH experiments proved the marker to be an analphoid 12pter derived isochromosome. Microdissection of the marker followed by reverse painting and array CGH analysis showed that the isochromosome contains approximately 6 Mb of 12pter-12p13.

Three cases with rare interstitial rearrangements of chromosome 1 characterized by multicolor banding.

In this report, we describe three unrelated patients with similar symptoms such as mental retardation, growth delay and multiple phenotypic abnormalities. GTG-banding analysis revealed karyotypes with add(1p) in two cases and an add(1q) in the third. Fluorescence in situ hybridization (FISH) analysis using high resolution multicolor banding (MCB) characterized the aberrations of the abnormal chromosomes 1 as a (sub)terminal duplication and inverted duplications, respectively.

Pallister-Killian syndrome: rapid decrease of isochromosome 12p frequency during amniocyte subculturing. Conclusion for strategy of prenatal cytogenetic diagnostics.

Pallister-Killian syndrome (PKS) is characterized cytogenetically by mosaic tetrasomy of chromosome 12p. Routine prenatal diagnosis of PKS is still complicated because of the difficulties of discriminating between the supernumerary isochromosome 12p and the duplication 21q and because of the variable level of mosaicism. The frequency of cells with an extra metacentric chromosome i(12)(p10) is usually determined by tissue-limited or tissue-specific mosaicism.

Two further AHO-like syndrome patients with deletion of glypican 1 gene region in 2q37.2-q37.3.

In this report, we describe two unrelated patients with mental retardation and brachydactyly E classified as patients suffering from Albright hereditary osteodystrophy-like (AHO-like) syndrome. Fluorescence in situ hybridization (FISH) analysis using 8 different subtelomeric probes in 2q36-37 proved that the patients had subtelomeric 2qter deletions of similar size. The recently proposed candidate gene glypican 1 (GPC1) is deleted in both reported patients.