Complex Variant of Philadelphia Translocation Involving Chromosomes 9, 12, and 22 in a Case with Chronic Myeloid Leukaemia

Chronic myeloid leukemia (CML) is a hematopoietic stem cell disorder included in the broader diagnostic category of myeloproliferative neoplasms, associated with fusion by BCR gene at chromosome 22q11 to ABL1 gene at chromosome 9q34 with the formation of the Philadelphia (Ph) chromosome. In 2–10% of CML cases, the fusion gene arises in connection with a variant translocation, involving chromosomes 9, 22, and one or more different chromosomes; consequently, the Ph chromosome could be masked within a complex chromosome rearrangement. In cases with variant Ph translocation a deletion on der(9) may be more frequently observed than in cases with the classical one. Herein we describe a novel case of CML with complex variant Ph translocation involving chromosomes 9, 12, and 22. We present the hematologic response and cytogenetic response after Imatinib treatment. We also speculated the mechanism which had originated the chromosome rearrangement

Interpreting mosaicism in chorionic villi: results of a monocentric series of 1001 mosaics in chorionic villi with follow-up amniocentesis

OBJECTIVES: Chromosomal mosaicism in chorionic villi (CV) is detected in ~1-2% of cases. When a mosaic in CV is detected during prenatal diagnosis, a confirmatory karyotype should be performed on amniocytes to discriminate between a mosaic confined to the placenta [confined placental mosaicism (CPM)] and one generalized to the fetus [true fetal mosaicism (TFM)]. We determined the likelihood that any mosaic abnormalities identified through CV samples are confirmed in the fetus. METHODS: Over a period of 14 years, the laboratory analyzed both the cytotrophoblast and the mesenchyme of 60 347 CV samples. Cytogenetic results from CV samples showing mosaicism with follow-up amniocentesis were considered. The incidence of CPM and TFM and the risk of confirmation in the amniotic fluid (AF) were calculated. Uniparental disomy (UPD) was tested on ~300 cases at risk due to involvement of an imprinted chromosome. RESULTS: Overall, 1317 mosaic CV cases (2.18%) were detected, of which 1001 were subsequently investigated by amniocentesis. The overall risk of TFM was 13% and UPD incidence was 2.1%. CONCLUSIONS: The very large presented sample set and consistency in cytogenetic methodology, especially the analysis of both placental layers performed on all CV samples will enable genetic counselors to determine the risk of fetal involvement and the clinical relevance of an identified mosaic condition

Confirmation of mosaicism and uniparental disomy in amniocytes, after detection of mosaic chromosome abnormalities in chorionic villi

Chromosome mosaicism is detected in about 1-2% of chorionic villi samples (CVS), and may be due to a postzygotic nondisjunction event generating a trisomic cell line in an initially normal conceptus (mitotic origin) or the postzygotic loss of one chromosome in an initially trisomic conceptus (meiotic origin and trisomy rescue). Depending on the distribution of the abnormal cell line, the mosaic can be confined to the placenta (CPM) or generalised to the fetus (TFM, true fetal mosaicism). Trisomy rescue could theoretically be associated with a 33.3% probability of uniparental disomy (UPD) in the fetus. The aim of this study was to determine the risk of fetal involvement in a cohort of numerical and structural chromosome mosaics revealed in chorionic villi by means of combined direct and long-term culture analyses; we also determined the incidence of UPD associated with mosaic aneuploidies and supernumerary markers involving imprinted chromosomes. A total of 273 of a consecutive series of 15 109 CVS evaluated during a period of 5 years showed a mosaic condition in direct preparations and/or long-term cultures; confirmatory amniocentesis was performed in 203 cases. The abnormal cell line was extended to the fetus in 12.8% cases in terms of structural and numerical abnormalities involving autosomes and sex chromosomes; the risk of TFM varied and depended on the placental tissue distribution of the abnormal cell line. One of the 51 cases in which the mosaic involved an imprinted chromosome showed UPD, thus indicating a risk of 1.96%

Prenatal BACs-on-Beads (TM): the prospective experience of five prenatal diagnosis laboratories

Objective We previously reported on the validation of Prenatal BACs-on-Beads (TM) on retrospectively selected and prospective prenatal samples. This bead-based multiplex assay detects chromosome 13, 18, 21 and X/Y aneuploidies and the nine most frequent microdeletion syndromes. We demonstrated that Prenatal BACs-on-Beads (TM) is a new-generation, prenatal screening tool. Here, we describe the experience of five European prenatal diagnosis laboratories concerning the ongoing use of Prenatal BACs-on-Beads (TM). Methods Some 1653 samples were analyzed. All results were confirmed by conventional karyotyping or another appropriate technique. All indications for invasive prenatal diagnosis were included. Amniotic fluid and chorionic villus samples were analyzed in equivalent proportions. Results The failure rate was 3.3% and the overall abnormality detection rate was similar to 1/10. Eighty-five percent of the detected abnormalities were common aneuploidies. Eleven microdeletions and duplications were identified, thus giving an overall yield for microdeletion and microduplication detection of 1/145. Compared with QF-PCR, Prenatal BACs-on-Beads (TM) provides an additional detection rate of similar to 1/250 for low-risk pregnancies. The false positive and negative rates were both <1%. Conclusion When associated with conventional karyotyping, the Prenatal BACs-on-Beads (TM) assay combines a short turnaround time (typical of rapid aneuploidy detection tests) with valuable detection of the most frequent microdeletion syndromes that cannot be detected in cytogenetic analyses. (C) 2012 John Wiley & Sons, Ltd

Chromosome abnormalities investigated by non-invasive prenatal testing account for approximately 50% of fetal unbalances associated with relevant clinical phenotypes.

During the past 20 years non-invasive screening tests have been increasingly utilized in prenatal diagnosis (PD) practice. Considerable effort has been exerted by multicenter consortia to evaluate the reliability of non-invasive screening tests in detecting those women with an increased risk of having a pregnancy affected by trisomies 21, 18, and 13, monosomy X, and triploidies. To what extent this group of abnormal karyotypes accounts for the total number of phenotypically relevant fetal chromosome abnormalities has, however, never been investigated. The present report is an attempt aimed to quantify this proportion. A retrospective analysis of a homogeneous survey of 115,128 consecutive invasive prenatal tests was undertaken. All cases were classified in accordance with the indication given for the invasive testing. Cytogenetic results regarding 96,416 karyotype analyses performed because of advanced maternal age (>or=35 years) or gestational anxiety (50% in women >or=35 years (65.1% and 61.8%, respectively). To conclude, approximately 50% of the phenotypically relevant abnormal karyotypes cannot be detected by non-invasive prenatal screening tests

Incidence of sex chromosome aneuploidy in Northern Italy: 27-year longitudinal study

OBJECTIVES: The availability of cell-free DNA (cfDNA) as a screening tool affords an opportunity for non-invasive identification of sex chromosome aneuploidies (SCAs). This longitudinal study from 1995 through 2021 investigates both the evolution and frequency of prenatal diagnostic testing using amniocentesis (AF) and chorionic villus sampling (CV), and the detection of SCAs through cfDNA samples from a large cohort in Northern Italy. METHODS: The results of genetic testing from CV and AF samples collected from public and private centers in Italy from 1995 to 2021 were collected. Chromosomal analysis was performed by routine Q-banding karyotype. Regression analyses and descriptive statistics were used to determine population data trends regarding the frequency of prenatal diagnostic testing and the identification of SCAs and correlated with changes in the indications for prenatal diagnostic tests and available screening options. RESULTS: In 27 years, 13,939,526 births and 231,227 invasive procedures were performed. This resulted in the prenatal diagnosis of 934 SCAs. After the commercial introduction of cfDNA use in 2015, the frequency of invasive procedures significantly decreased (P=0.03), while the frequency of prenatal SCA detection significantly increased (P=0.007). The indication for invasive procedures also shifted from advanced maternal age (AMA) to positive cfDNA results for sex chromosome trisomies (SCTs). CONCLUSIONS: Our findings suggest the inclusion of SCAs in prenatal cfDNA screening tests can increase the prenatal identification of affected individuals. As the benefits of early ascertainment are increasingly recognized, it is essential that healthcare providers are equipped with comprehensive and evidence-based information regarding the associated phenotypic differences and the availability of targeted effective interventions to improve neurodevelopmental and health outcomes for affected individuals. This article is protected by copyright. All rights reserved