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Samuel A Latt - One of the best experts on this subject based on the ideXlab platform.

  • use of y Chromosome specific probes to detect low level sex Chromosome Mosaicism
    Clinical Genetics, 2008
    Co-Authors: Umadevi Tantravahi, Diana W Bianchi, Christine Haley, Margaret M Destrempes, Alyne T Ricker, Bruce R Korf, Samuel A Latt
    Abstract:

    An individual, found to be a true hermaphrodite at laparotomy, is presented. Cytogenetic studies which initially disclosed a 46,XX karyotype, conflicted with the anatomic presence of a testis. More extensive analysis of peripheral lymphocytes and skin fibroblasts revealed low level 46,XX/69,XXY Mosaicism. DNA hybridization studies, using highly repeated Y Chromosome specific probes, confirmed the rare presence of Y Chromosome bearing cells. Such combined clinical and molecular studies can have an important impact on diagnosis and management of cases in which sex Chromosome Mosaicism is suspected.

Marc De Braekeleer - One of the best experts on this subject based on the ideXlab platform.

  • a study of aneuploidy and dna fragmentation in spermatozoa of three men with sex Chromosome Mosaicism including a 45 x cell line
    Human Fertility, 2015
    Co-Authors: Minh Nguyen, Frédéric Morel, Louis Bujan, Pascale Maypanloup, Marc De Braekeleer, A Perrin
    Abstract:

    AbstractMeiotic segregation of mosaic males with a 45,X cell line has been little examined. In this study, we evaluated the risk of aneuploid gametes using fluorescence in situ hybridization (FISH) and DNA fragmentation in ejaculated spermatozoa of three men with sex Chromosome Mosaicism including a 45,X cell line. Triple- and dual-color FISH were performed. Sperm DNA fragmentation was detected using the TUNEL assay. A significantly increased frequency of XY disomic spermatozoa was observed for patients (P)1 and P2. A significant increase in diploidy and autosomal aneuploidy was found in P2 and P3, respectively. The rate of DNA fragmentation was not different from that observed in a control group. Data from the literature are scarce (only 3 cases reported), making comparison of the present data difficult, especially as the frequencies of the cell lines comprising the Mosaicism differed between patients. Furthermore, the proportion of the different cell lines can differ from one tissue to another in the sa...

  • 45,X/46,XX Mosaicism below 30% of aneuploidy: clinical implications in adult women from a reproductive medicine unit.
    European Journal of Endocrinology, 2010
    Co-Authors: Lionel Homer, V. Amice, Marie-thérèse Le Martelot, F. Morel, Véronique Kerlan, Michel Collet, Marc De Braekeleer
    Abstract:

    OBJECTIVE: Turner's syndrome (TS) is well known, but prognosis for 45,X/46,XX Mosaicism below 30% of aneuploidy has not been established. We evaluated differences in clinical features and biological parameters between patients with numerical sex Chromosome Mosaicism diagnosed incidentally and control women. DESIGN: Retrospective observational study of clinical features and biological parameters. METHODS: Standard endocrinological and gynecological examination was done and early-follicular-phase blood values were collected from the medical records of women aged 21-43, who were referred to our ward from 1996 to 2006 because of infertility and were karyotyped. Seventy-one women with sex Chromosome Mosaicism (45,X/46,XX) ranging from 4 to 28% were assigned a chromosomally normal woman (46,XX) matched according to age (n=71). RESULTS: In group 45,X/46,XX, 8% or more of aneuploidy accounted for a smaller height compared to controls (P=0.01). Body mass index was increased from 6% of aneuploidy (P=0.02) and was positively correlated to the percentage of 45,X cells (P=0.0001); menarche occurred earlier from 10% of aneuploidy (P=0.01) and was inversely correlated to the percentage of 45,X cells (P=0.045). No difference was found between the groups for FSH, LH, estradiol, inhibin B, and TSH values. Spontaneous abortions were more frequent in case of Mosaicism (P=0.01), and recurrence was positively correlated to the percentage of aneuploidy (P=0.008). CONCLUSION: Sex Chromosome Mosaicism is responsible for clinical changes from 6% of aneuploidy, corresponding to the main phenotypical features of TS.

Raoul C M Hennekam - One of the best experts on this subject based on the ideXlab platform.

  • leopard syndrome with partly normal skin and sex Chromosome Mosaicism
    American Journal of Medical Genetics Part A, 2007
    Co-Authors: Karin Writzl, Erik A Sistermans, Jan M.n. Hoovers, Raoul C M Hennekam
    Abstract:

    We report on a family with LEOPARD syndrome which was molecularly proven (p.Thr468Met in PTPN11) in a father and his adult son. The father had multiple lentigines dispersed equally over his body; the son was similarly affected except for the left part of thorax, back and left arm, which were completely devoid of lentigines and only showed a few nevi. In addition, the son was found to have a mosaic karyotype, 47,XYY/46,XY, in lymphocytes. Skin biopsies from the pigmented and unpigmented forearm showed that mainly a 47,XYY karyotype was present in the pigmented skin and mainly a 46,XY karyotype in the unpigmented skin. In both fibroblast cultures the PTPN11 mutation was present, and no additional mutation could be detected. We discuss the various possible explanations for this phenotype, which include the possibility of coincidence; revertant Mosaicism; silencing of a second PTPN11 mutation; gene(s) located on a sex Chromosome influencing the phenotype; and epigenetic influences. We favor that the co-occurrence of a sex Chromosome Mosaicism and Mosaicism for skin symptoms in a single patient with LEOPARD syndrome is coincidence, but that Mosaicism for LEOPARD skin symptoms in itself may well be more frequent and needs additional studies. Each of the above-hypothesized mechanisms may then remain possible.

Daniel L. Van Dyke - One of the best experts on this subject based on the ideXlab platform.

  • Testing for sex Chromosome Mosaicism in Turner syndrome
    International Congress Series, 2006
    Co-Authors: Daniel L. Van Dyke, Anne E. Wiktor
    Abstract:

    Abstract Ullrich–Turner syndrome (UTS) is frequently associated with chromosomal Mosaicism. Conventional cytogenetic studies identify sex Chromosome Mosaicism in approximately 55% of patients. Roughly 2% of UTS patients who are mosaic exhibit a cell population with 46,XY or a structural rearrangement of the Y Chromosome. Such patients are at an increased risk of gonadoblastoma and occasionally more clinically significant gonadal tumors. For UTS patients with a monosomy X karyotype result, we developed and validated a FISH assay to identify low level Mosaicism for an XY or XX cell population, or an X or Y structural rearrangement. We have tested 44 patients with monosomy X for sex chromosomal Mosaicism using FISH. A second cell line was identified in 10 patients (23%), 6 with X/XX, 1 X/i(X), and 3 X/dic(X). None of the patients studied thus far with FISH have exhibited a Y-Chromosome cell population. FISH as an adjunct to karyotype analysis is useful to identify sex Chromosome Mosaicism in UTS patients, and has increased the rate of identification of Mosaicism from 55% to 67%.

  • detection of low level sex Chromosome Mosaicism in ullrich turner syndrome patients
    American Journal of Medical Genetics Part A, 2005
    Co-Authors: Anne E. Wiktor, Daniel L. Van Dyke
    Abstract:

    Ullrich-Turner syndrome (UTS) is most commonly due to a 45,X Chromosome defect, but is also seen in patients with a variety of X-Chromosome abnormalities or 45,X/46,XY Mosaicism. The phenotype of UTS patients is highly variable, and depends largely on the karyotype. Patients are at an increased risk of gonadoblastoma when a Y-derived Chromosome or Chromosome fragment is present. Since constitutional Mosaicism is present in approximately 50% of UTS patients, the identification of minor cell populations is clinically important and a challenge to laboratories. We identified 50 females with a 45,X karyotype as the sole abnormality or as part of a more complex karyotype. Twenty two (44%) had a 45,X karyotype; Mosaicism for a second normal or structurally abnormal X was observed in 24 (48%) samples, and Mosaicism for Y chromosomal material in 4 (8%) cases. To further investigate the possibility of Mosaicism in the 22 patients with an apparently non-mosaic 45,X karyotype, we performed FISH using centromere probes for the X and Y Chromosomes. A minor XX cell line was identified in 3 patients, and the 45,X result was confirmed in 19 samples. No samples with XY Mosaicism were identified. We describe our validation process for a FISH assay to be used in clinical practice to identify XX or XY Mosaicism. FISH as an adjunct to karyotype analysis provides a sensitive and cost-effective technique to identify sex Chromosome Mosaicism in UTS patients.

  • incidence and significance of Chromosome Mosaicism involving an autosomal structural abnormality diagnosed prenatally through amniocentesis a collaborative study
    Prenatal Diagnosis, 1996
    Co-Authors: Lillian Y. F. Hsu, Daniel L. Van Dyke, Kathleen E Richkind, Barbara F Crandall, Debra Saxe, Gabriel S Khodr, Michael T Mennuti, Gail Stetten, Wayne A Miller, Jean H Priest
    Abstract:

    Among 179,663 prenatal diagnosis cases collected from ten institutions and two publications, 555 (0.3 per cent) were diagnosed as having Chromosome Mosaicism. Of these, 57 (10.3 per cent) were mosaic for an autosomal structural abnormality, 28 (5 per cent) for a sex Chromosome structural abnormality, and 85 (15.3 per cent) were mosaic for a marker Chromosome. Ninety-five cases of prenatally diagnosed Mosaicism with a structural abnormality in an autosome and a normal cell line, and with a known phenotypic outcome, were collected for karyotype-phenotype correlations through our collaboration (40 cases), a prior survey (26 cases), and published reports (29 cases). They included 13 balanced reciprocal translocations, one unbalanced reciprocal translocation, four balanced Robertsonian translocations, four unbalanced Robertsonian translocations, four inversions, 17 deletions, three ring Chromosomes, 19 i(20q), seven +i(12p), six other isoChromosomes, and 17 partial trisomies resulting from a duplication or other rearrangement. All cases mosaic for a balanced structural rearrangement resulted in a normal phenotype. All cases of 46/46,i(20q) resulted in normal liveborns. Five of seven cases with 46/47,+i(12p) had an abnormal phenotype compatible with Killian-Pallister syndrome. The overall risk for an abnormal outcome for a mosaic case with an unbalanced structural abnormality, excluding 46/46,i(20q) and 46/47,+i(12p), is 40.4 per cent. In the same category, the study also suggested a correlation between the percentage of abnormal cells and an abnormal phenotype. For Mosaicism involving a terminal deletion, the possibility of a familial fragile site should be considered.

Magdalena Zernickagoetz - One of the best experts on this subject based on the ideXlab platform.

  • autophagy mediated apoptosis eliminates aneuploid cells in a mouse model of Chromosome Mosaicism
    Nature Communications, 2020
    Co-Authors: Shruti Singla, Lisa K Iwamotostohl, Meng Zhu, Magdalena Zernickagoetz
    Abstract:

    The high incidence of aneuploidy in the embryo is considered the principal cause for low human fecundity. However, the prevalence of aneuploidy dramatically declines as pregnancy progresses, with the steepest drop occurring as the embryo completes implantation. Despite the fact that the plasticity of the embryo in dealing with aneuploidy is fundamental to normal development, the mechanisms responsible for eliminating aneuploid cells are unclear. Here, using a mouse model of Chromosome Mosaicism, we show that aneuploid cells are preferentially eliminated from the embryonic lineage in a p53-dependent process involving both autophagy and apoptosis before, during and after implantation. Moreover, we show that diploid cells in mosaic embryos undertake compensatory proliferation during the implantation stages to confer embryonic viability. Together, our results indicate a close link between aneuploidy, autophagy, and apoptosis to refine the embryonic cell population and ensure only chromosomally fit cells proceed through development of the fetus.

  • mouse model of Chromosome Mosaicism reveals lineage specific depletion of aneuploid cells and normal developmental potential
    Nature Communications, 2016
    Co-Authors: Helen Bolton, Sarah J L Graham, Niels Van Der Aa, Parveen Kumar, Koen Theunis, Elia Fernandez Gallardo, Thierry Voet, Magdalena Zernickagoetz
    Abstract:

    Most human pre-implantation embryos are mosaics of euploid and aneuploid cells. To determine the fate of aneuploid cells and the developmental potential of mosaic embryos, here we generate a mouse model of Chromosome Mosaicism. By treating embryos with a spindle assembly checkpoint inhibitor during the four- to eight-cell division, we efficiently generate aneuploid cells, resulting in embryo death during peri-implantation development. Live-embryo imaging and single-cell tracking in chimeric embryos, containing aneuploid and euploid cells, reveal that the fate of aneuploid cells depends on lineage: aneuploid cells in the fetal lineage are eliminated by apoptosis, whereas those in the placental lineage show severe proliferative defects. Overall, the proportion of aneuploid cells is progressively depleted from the blastocyst stage onwards. Finally, we show that mosaic embryos have full developmental potential, provided they contain sufficient euploid cells, a finding of significance for the assessment of embryo vitality in the clinic.