Ocena prawdopodobieństwa urodzenia dziecka z niezrównoważonym kariotypem oraz ryzyka wystąpienia rożnych patologii ciąży w rodzinach nosicieli translokacji chromosomowych wzajemnych angażujących chromosom 7

Introduction: Carriership of reciprocal chromosomal translocation (RCT) may be the reason the occurrence of congenital malformations in the offspring, early neonatal death, stillbirth, and recurrent miscarriages due to unbalanced karyotype of gametes. The probability rate for individual categories of unfavorable outcomes depends on the kind of chromosome involved and is individually variable. Objectives: The aim of study was to estimate the probability rates for unbalanced offspring and to evaluate the risk for different categories of unfavorable pregnancy outcomes, depending on the size of chromosomal segment with differentiation between maternal/paternal origin of the reciprocal chromosomal translocations involving chromosome 7p (RCT-7p) and 7q (RCT-7q). In addition, the use of the obtained results has been illustrated by the example of a family with unique RCT t(7;9)(p21.3,p23). Material and methods: Empirical and cytogenetic data on 341 pregnancies and offspring of 133 carriers were collected from 69 pedigrees of carriers of RCT-7p and RCT-7q at risk for a single 7 segment imbalance. The probability rates of particular form of pregnancy pathology have been calculated according to the method of Stengel-Rutkowski and Stene, including all forms of meiotic segregation and their survival rates after fertilization to term childbirth. Results: The probability rates for unbalanced offspring for carriers of RCT-7p after 2:2 disjunction and adjacent-1 segregation were calculated as 5.5%±2.2% (6/108); for maternal (MAT) and paternal (PAT) carriers were aboutCel pracy: Celem pracy było opracowanie wskaźników prawdopodobieństwa urodzenia dziecka z niezrównoważonym kariotypem oraz wskaźników ryzyka różnych patologii ciąży w rodzinach nosicieli translokacji chromosomowych wzajemnych angażujących segmenty chromosomu 7 (TCW-7), w zależności od długości pojedynczych segmentów krótkich (TCW-7p) i długich (TCW-7q) ramion chromosomu 7, z uwzględnieniem rodzicielskiego pochodzenia nosicielstwa. Na przykładzie rodziny z nosicielstwem unikatowej t(7;9)(p21.3;p23) zaprezentowano, w jaki sposób praktycznie można wykorzystać uzyskane wskaźniki udzielając porady genetycznej. Materiał i metody: Analizę segregacyjną przeprowadzono w grupie 69 rodowodów nosicieli TCW-7 zawierających dane kliniczne i cytogenetyczne 341 ciąż i urodzeń potomstwa w sześciu grupach oddzielnie w zależności od długości segmentu 7p i 7q wyznaczonej przez położenie punktu złamania TCW: 7p21→pter, 7p14…p15→pter, 7p11…p12…p13→pter oraz 7q33…q34…q35→qter, 7q32 →qter, 7q11…q21.. q22…q31→qter z uwzględnieniem rodzicielskiego pochodzenia TCW. Wyniki: Prawdopodobieństwo urodzenia dziecka z niezrównoważonym kariotypem w przypadku nosicielstwa TCW-7p wynosiło 5.5±2.2% (6/108) (w tym matczyne MAT

Diagnostyka prenatalna płodu ze wspólnym kanałem przedsionkowo-komorowym i delecją chromosomu 8 (pter→p21).

Summary Congenital heart malformations, detected during a pregnancy, are associated in 20-48% of cases with a chromosomal aberration. In the following study we have reported the deletion of chromosome 8 (pter→p21), diagnosed prenatally at 22 weeks of gestation, because of a visible defect in the upper part of the interventricular septum and a partial defect of the atrial septum. The atria and the ventricles were joined with a common central valve. The cordocentesis was performed and karyotype: 46, XX ish del(8)(wcp8x2) was detected. Because of the persistent bradycardia of the foetus, indicating a danger of intrauterine asphyxia of the foetus, as well as features of premature placental detachment, the caesarean section was performed at 27 weeks of gestation. The patient gave birth to a daughter weighing 960 g. The child died in the 4th hour of her life. On the basis of the present observation it is safe to say that when an AV-canal defect is diagnosed prenatally, special attention must be paid to the detection of chromosomal abnormalities and amniocentesis or cordocentesis should be performed to assess the state of affairs.Streszczenie Wrodzone wady serca wykrywane podczas ciąży w 20-48% związane są z aberracjami chromosomowymi. Opisano przypadek płodu z delecją chromosomu 8 (pter→p21) zdiagnozowana w 22 tygodniu, u którego w badaniu usg stwierdzono ubytek w górnej części przegrody międzykomorowej i częściowy ubytek przegrody międzyprzedsionkowej. Przedsionki i komory łączyła wspólna zastawka centralna. Wykonano kordocentezę. W badaniu cytogenetycznym określono kariotyp płodu: 46, XX ish del(8)(p21)(wcp8x2)[31] - delecja fragmentu ramion krótkich (p) chromosomu 8 prowadzącą do częściowej monosomii chromosomu 8 od prążka p21do pter. Ze względu na zaburzenia w tętnie płodu pod postacią utrzymującej się bradykardii płodu do 60 uderzeń/minutę w zapisie kardiotokograficznym, wskazujące na zagrażającą zamartwicę wewnątrzmaciczną płodu oraz cechy przedwczesnego oddzielenia łożyska, ciążę ukończono drogą cięcia cesarskiego w 27 tygodniu. Pacjentka urodziła córkę o masie 960g. Dziecko zmarło w 4 godzinie życia. W przypadku wystąpienia wspólnego kanału przedsionkowokomorowego u płodu trzeba zwrócić uwagę na możliwość istnienia aberracji chromosomowych i należy wykonać amniopunkcję lub kordocentezę celem oceny kariotypu płodu

Bidirectionality and transcriptional activity of the EWSR1 promoter region

EWSR1 is involved in chimeric proteins which play crucial roles in the development of a variety of bone and soft tissue tumors. Many of the chimeric genes involving EWSR1 have been extensively studied, whereas less is known about the wild-type (wt) gene and its regulation. As the expression of the chimeric gene is driven by the EWSR1 promoter, it is of importance to study the mechanisms regulating wt EWSR1 expression. We estimated the transcriptional activity of the EWSR1 promoter through deletion fragments driving reporter gene expression. This assay identified the 100-bp region immediately downstream of the EWSR1 transcriptional start site (+1) and the downstream region from +100 to +300 as important regions for transcriptional regulation. We also found that EWSR1 and RHBDD3, a gene located directly upstream of EWSR1 that is likely to share regulatory elements with EWSR1, were co-expressed in the tissue panels, Ewing tumor biopsies and cell lines. Thus, our results show that the EWSR1 promoter functions in a bidirectional manner, thereby regulating also RHBDD3, and identifies specific regions that strongly influence promoter activity

Clinical and Biological Significance of <i>ESR1</i> Gene Alteration and Estrogen Receptors Isoforms Expression in Breast Cancer Patients

The amplification of estrogen receptor alpha (ER&#945;) encoded by the ESR1 gene has been described as having a prognostic role in breast cancer patients. However, increased dosage of the ESR1 gene (tested by real-time PCR) is also observed in ER-negative breast cancers, which might suggest the expression of alternative isoforms of ER&#945; (other than classical ER&#945; of 66 kDa). In the current work, we have investigated the ESR1 gene dosage in 402 primary breast cancer patients as well as the expression of ER&#945; isoforms&#8212;ER&#945;66 and ER&#945;36&#8212;on mRNA and protein levels. The obtained results were correlated with clinicopathological data of the patients. Results showed that increased ESR1 gene dosage is not related to ESR1 gene amplification measured by fluorescent in situ hybridization (FISH), but it correlates with the decreased expression of ER&#945;66 isoform (p = 0.01). Interestingly, the short ER isoform ER&#945;36 was expressed in samples with increased ESR1 gene dosage, suggesting that genomic aberration might influence the expression of that particular isoform. Similarly to ESR1 increased gene dosage, high ER&#945;36 expression was linked with the decreased disease-free survival of the patients (p = 0.05), which was independent of the status of the classical ER&#945;66 level in breast tumors

Additional file 1: Table S1. of Application of high-resolution genomic profiling in the differential diagnosis of liposarcoma

Clinicopathological data of the liposarcoma samples included in the study. (DOCX 21 kb

Additional file 2: Table S2. of Application of high-resolution genomic profiling in the differential diagnosis of liposarcoma

Karyotypes and DNA copy number changes established by array-CGH in 66 liposarcoma tumors. (DOCX 44 kb

Personalized health risk assessment based on single-cell RNA sequencing analysis of a male with 45, X/48, XYYY karyotype

Abstract Numeric sex chromosome abnormalities are commonly associated with an increased cancer risk. Here, we report a 14-year-old boy with a rare mosaic 45, X/48, XYYY karyotype presenting with subtle dysmorphic features and relative height deficiency, requiring growth hormone therapy. As only 12 postnatal cases have been described so far with very limited follow-up data, to assess the proband’s long-term prognosis, including cancer risk, we performed high-throughput single-cell RNA sequencing (scRNA-seq) analysis. Although comprehensive cytogenetic analysis showed seemingly near perfect balance between 45, X and 48, XYYY cell populations, scRNA-seq revealed widespread differences in genotype distribution among immune cell fractions, specifically in monocytes, B- and T-cells. These results were confirmed at DNA level by digital-droplet PCR on flow-sorted immune cell types. Furthermore, deregulation of predominantly autosomal genes was observed, including TCL1A overexpression in 45, X B-lymphocytes and other known genes associated with hematological malignancies. Together with the standard hematological results, showing increased fractions of monocytes and CD4+/CD8+T lymphocytes ratio, long-term personalized hemato-oncological surveillance was recommended in the reported patient