Low-Level Trisomy 14 Mosaicism: A Carrier of an Isochromosome 14 and a Supernumerary Marker Chromosome 14

2020 ◽  
pp. 1-7
Author(s):  
Voula Velissariou ◽  
Francis Sachinidi ◽  
Stavroula Christopoulou ◽  
Lina Florentin ◽  
Thomas Liehr ◽  
...  
Keyword(s):  
Cell Lines ◽  
De Novo ◽  
Marker Chromosome ◽  
Uniparental Disomy ◽  
Chorionic Villus ◽  
Copy Number Variations ◽  
Oligonucleotide Array ◽  
Chorionic Villus Sampling ◽  
Chromosome 14 ◽  
Different Tissues

Trisomy 14 (T14) mosaicism is a rare chromosomal condition characterised by various clinical features, including developmental delay, growth impairment, and dysmorphism. Here, we report on a 12-year-old female referred for cytogenetic analysis due to short stature. Standard GTG-banding analysis on the patient’s peripheral blood revealed mosaic Τ14 in the form of an i(14)(q10) in 3% of cells. Furthermore, a small supernumerary marker chromosome (sSMC) had been detected in the first trimester of pregnancy in chorionic villus sampling. A skin biopsy in the patient revealed the presence of a metacentric sSMC in 100% of cells. Cytogenetic and FISH studies showed that it was a de novo metacentric bisatellited sSMC derived from chromosomes 14 or 22. Oligonucleotide array-CGH using skin cells revealed no copy number variations. Studies for uniparental disomy 14 by microsatellite analysis confirmed biparental inheritance. To the best of our knowledge, this is the second report of a patient with 2 abnormal cell lines involving chromosome 14 in different tissues, one with mosaic T14 in the form of i(14)(q10) and one with an sSMC derived from chromosome 14, present in blood and skin, respectively. A rare mechanism of trisomy rescue events is proposed to explain the presence of the different cell lines in the tissues examined. This case highlights the importance of providing the cytogenetics laboratory with adequate clinical data to test for low mosaicism and analyse different tissues if necessary, thus contributing to the suitable clinical management of the patient.

PRENATAL DETECTION OF TWO DIFFERENT MONOSOMIC CELL LINES BY CHORIONIC VILLUS SAMPLING

1996 ◽  
Vol 16 (2) ◽  
pp. 169-172 ◽  
Author(s):  
TE-YAO HSU ◽  
JUI-DER LIOU ◽  
JOSHUA A. COPEL ◽  
MAURICE J. MAHONEY ◽  
W. ROY BREG ◽  
...  
Keyword(s):  
Cell Lines ◽  
Chorionic Villus ◽  
Chorionic Villus Sampling ◽  
Prenatal Detection

scholarly journals Maternal Uniparental Disomy for Chromosome 14

1996 ◽  
Vol 45 (1-2) ◽  
pp. 169-172 ◽  
Author(s):  
D.A. Coviello ◽  
E. Panucci ◽  
M.M. Mantero ◽  
C. Perfumo ◽  
M. Guelfi ◽  
...  
Keyword(s):  
Robertsonian Translocation ◽  
De Novo ◽  
Clinical Phenotype ◽  
Uniparental Disomy ◽  
Chromosome 14 ◽  
Motor Delay ◽  
Maternal Uniparental Disomy ◽  
Severe Scoliosis ◽  
Severe Hypotonia

AbstractA girl carrying a de novo balanced 13-14 robertsonian translocation showed a clinical phenotype with severe hypotonia, hyperextensible joints, frontal bossing, asymmetric face, no mental retardation, severe scoliosis and motor delay. In situ hybridization analysis on chromosome spreads revealed the presence of the two centromeres in the rearranged chromosomes. Molecular analysis on genomic DNA showed the presence in the proposita of two chromosomes 14 of maternal origin and no chromosome 14 from the father indicating a maternal monocentric uniparental disomy for chromosome 14 (mUPD14). Our patient shows several similarities with other reported cases of mUPD14, suggesting imprinting of a region(s) of chromosome 14 and defining a possible mUPD14 Syndrome.

scholarly journals Decreased Placental FPR2 in Early Pregnancies That Later Developed Small-For-Gestation Age: A Potential Role of FPR2 in the Regulation of Epithelial-Mesenchymal Transition

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 921 ◽  
Author(s):  
Padma Murthi ◽  
Gayathri Rajaraman ◽  
Jan Jaap H.M. Erwich ◽  
Evdokia Dimitriadis
Keyword(s):  
Cell Lines ◽  
Target Genes ◽  
Epithelial Mesenchymal Transition ◽  
Chorionic Villus ◽  
Formyl Peptide Receptor ◽  
Chorionic Villus Sampling ◽  
Mesenchymal Transition ◽  
Peptide Receptor ◽  
Gestation Age ◽  
Gene And Protein Expression

We reported earlier that an anti-inflammatory small peptide receptor-formyl peptide receptor-2 (FPR2) was significantly decreased in placentas from third trimester pregnancies complicated with fetal growth restriction (FGR), compared to placentas from uncomplicated control pregnancies, suggesting FPR2 may play a role in the development of FGR. The aim of this study is to investigate whether the actions of FPR2 alters placental growth process in humans. Accordingly, using small-for-gestation age (SGA) as a proxy for FGR, we hypothesize that FPR2 expression is decreased in first-trimester placentas of women who later manifest FGR, and contributes to aberrant trophoblast function and the development of FGR. Chorionic villus sampling (CVS) tissues were collected at 10–12 weeks gestation in 70 patients with singleton fetuses; surplus tissue was used. Real-time PCR and immunoassays were performed to quantitate FPR2 gene and protein expression. Silencing of FPR2 was performed in two independent, trophoblast-derived cell lines, HTR-8/SVneo and JEG-3 to investigate the functional consequences of FPR2 gene downregulation. FPR2 mRNA relative to 18S rRNA was significantly decreased in placentae from SGA-pregnancies (n = 28) compared with controls (n = 52) (p < 0.0001). Placental FPR2 protein was significantly decreased in SGA compared with control (n = 10 in each group, p < 0.05). Proliferative, migratory and invasive potential of the human placental-derived cell lines, HTR-8/SVneo and JEG-3 were significantly reduced in siFPR2 treated cells compared with siCONT control groups. Down-stream signaling molecules, STAT5B and SOCS3 were identified as target genes of FPR2 action in the trophoblast-derived cell lines and in SGA and control chorionic villous tissues. FPR2 is a novel regulator of key molecular pathways and functions in placental development, and its decreased expression in women destined to develop FGR reinforces a placental origin of SGA/FGR, and that it contributes to causing the development of SGA/FGR.

Two Abnormal Cell Lines of Trisomy 14 and t(X;14) with Skewed X-Inactivation

2020 ◽  
Vol 160 (3) ◽  
pp. 124-133
Author(s):  
Amal M. Mohamed ◽  
Maha M. Eid ◽  
Ola M. Eid ◽  
Shymaa H. Hussein ◽  
Aida M. Mossaad ◽  
...  
Keyword(s):  
Cell Lines ◽  
Buccal Mucosa ◽  
Gene Dosage ◽  
Uniparental Disomy ◽  
X Inactivation ◽  
Fish Analysis ◽  
Snp Analysis ◽  
Chromosome 14 ◽  
Skewed X Inactivation ◽  
Mosaic Trisomy

Trisomy 14 is incompatible with live, but there are several patients reported with mosaic trisomy 14. We aimed to study the pattern of X inactivation and its effect on a translocated autosome and to find out an explanation of the involvement of chromosome 14 in 2 different structural chromosomal abnormalities. We report on a girl with frontal bossing, hypertelorism, low-set ears, micrognathia, cleft palate, congenital heart disease, and abnormal skin pigmentations. The patient displayed iris, choroidal, and retinal coloboma and agenesis of the corpus callosum and cerebellar vermis hypoplasia. Cytogenetic analysis revealed a karyotype 45,X,der(X)t(X;14)(q24;q11)[85]/46,XX,rob(14;14)(q10;q10),+14[35]. Array-CGH for blood and buccal mucosa showed high mosaic trisomy 14 and an Xq deletion. MLPA detected trisomy 14 in blood and buccal mucosa and also showed normal methylation of the imprinting center. FISH analysis confirmed the cell line with trisomy 14 (30%) and demonstrated the mosaic deletion of the Xq subtelomere in both tissues. There was 100% skewed X inactivation for the t(X;14). SNP analysis of the patient showed no region of loss of heterozygosity on chromosome 14. Also, genotype call analysis of the patient and her parents showed heterozygous alleles of chromosome 14 with no evidence of uniparental disomy. Our patient had a severe form of mosaic trisomy 14. We suggest that this cytogenetic unique finding that involved 2 cell lines with structural abnormalities of chromosome 14 occurred in an early postzygotic division. These 2 events may have happened separately or maybe there is a kind of trisomy or monosomy rescue due to dynamic cytogenetic interaction between different cell lines to compensate for gene dosage.

scholarly journals Molecular characterization of a complex small supernumerary marker chromosome derived from chromosome 18p: an addition to the literature

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Eleonora Marchina ◽  
Michela Forti ◽  
Mariella Tonelli ◽  
Stefania Maccarini ◽  
Francesca Malvestiti ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Molecular Characterization ◽  
De Novo ◽  
Marker Chromosome ◽  
Uniparental Disomy ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Specific Syndrome ◽  
Trisomy 18P

Abstract Background Small supernumerary marker chromosomes (sSMC) are a heterogeneous group of structurally abnormal chromosomes, with an incidence of 0,044% in newborns that increases up to almost 7 times in developmentally retarded patients. sSMC from all 24 chromosome have been described, most of them originate from the group of the acrocentric, with around half deriving from the chromosome 15. Non-acrocentric sSMC are less common and, in the 30 percent of the cases, are associated with phenotypic effect. Complex sSMC consist of chromosomal material derived from more than one chromosome. Genotype–phenotype correlations in patients with sSMC are difficult to assess. Clinical features depend on factors such as its size, genetic content, the involvement of imprinted genes which may be influenced by uniparental disomy and the level of mosaicism. Trisomy of the short arm of chromosome 18 (18p) is an infrequent finding and does not appear to be associated with a specific syndrome. However, mild intellectual disability with or without other anomalies is reported in almost one-third of the patients. Case presentation Here we present clinical and molecular characterization of a new case of de novo complex sSMC consisting of the entire short arm of chromosome 18p associated with a centromere of either chromosome 13 or 21, evidenced in a 5-year-old boy during diagnostic workup for moderate intellectual disability and dysmorphisms. To date, only seven cases of isolated trisomy 18p due to a sSMC have been reported, three of which have been characterized by array CGH. In two of them the breakpoints and the size of the duplication have been described. In the manuscript we also reviewed cases reported in the DECIPHER database carrying similar duplication and also considered smaller duplications within the region of interest, in order to evaluate the presence of critical regions implicated in the pathological phenotype. Conclusions Our case provides additional information about phenotypic effects of pure trisomy 18p, confirms chromosomal microarray analysis as gold standard to characterize complex sSMC, and supplies additional elements for genetic counselling.

scholarly journals Identification of copy number variations and translocations in cancer cells from Hi-C data

2017 ◽  
Author(s):  
Abhijit Chakraborty ◽  
Ferhat Ay
Keyword(s):  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Copy Number ◽  
De Novo ◽  
3D Structure ◽  
Cancer Cell Lines ◽  
Copy Number Variations ◽  
Genomic Rearrangements ◽  
Link Type

AbstractMotivationEukaryotic chromosomes adapt a complex and highly dynamic three-dimensional (3D) structure, which profoundly affects different cellular functions and outcomes including changes in epigenetic landscape and in gene expression. Making the scenario even more complex, cancer cells harbor chromosomal abnormalities (e.g., copy number variations (CNVs) and translocations) altering their genomes both at the sequence level and at the level of 3D organization. High-throughput chromosome conformation capture techniques (e.g., Hi-C), which are originally developed for decoding the 3D structure of the chromatin, provide a great opportunity to simultaneously identify the locations of genomic rearrangements and to investigate the 3D genome organization in cancer cells. Even though Hi-C data has been used for validating known rearrangements, computational methods that can distinguish rearrangement signals from the inherent biases of Hi-C data and from the actual 3D conformation of chromatin, and can precisely detect rearrangement locations de novo have been missing.ResultsIn this work, we characterize how intra and inter-chromosomal Hi-C contacts are distributed for normal and rearranged chromosomes to devise a new set of algorithms (i) to identify genomic segments that correspond to CNV regions such as amplifications and deletions (HiCnv), (ii) to call inter-chromosomal translocations and their boundaries (HiCtrans) from Hi-C experiments, and (iii) to simulate Hi-C data from genomes with desired rearrangements and abnormalities (AveSim) in order to select optimal parameters for and to benchmark the accuracy of our methods. Our results on 10 different cancer cell lines with Hi-C data show that we identify a total number of 105 amplifications and 45 deletions together with 90 translocations, whereas we identify virtually no such events for two karyotypically normal cell lines. Our CNV predictions correlate very well with whole genome sequencing (WGS) data among chromosomes with CNV events for a breast cancer cell line (r=0.89) and capture most of the CNVs we simulate using Avesim. For HiCtrans predictions, we report evidence from the literature for 30 out of 90 translocations for eight of our cancer cell lines. Further-more, we show that our tools identify and correctly classify relatively understudied rearrangements such as double minutes (DMs) and homogeneously staining regions (HSRs).ConclusionsConsidering the inherent limitations of existing techniques for karyotyping (i.e., missing balanced rearrangements and those near repetitive regions), the accurate identification of CNVs and translocations in a cost-effective and high-throughput setting is still a challenge. Our results show that the set of tools we develop effectively utilize moderately sequenced Hi-C libraries (100-300 million reads) to identify known and de novo chromosomal rearrangements/abnormalities in well-established cancer cell lines. With the decrease in required number of cells and the increase in attainable resolution, we believe that our framework will pave the way towards comprehensive mapping of genomic rearrangements in primary cells from cancer patients using Hi-C.AvailabilityCNV calling: https://github.com/ay-lab/HiCnvTranslocation calling: https://github.com/ay-lab/HiCtransHi-C simulation: https://github.com/ay-lab/AveSim

scholarly journals Clinical significance and mechanisms associated with segmental UPD

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Peter R. Papenhausen ◽  
Carla A. Kelly ◽  
Samuel Harris ◽  
Samantha Caldwell ◽  
Stuart Schwartz ◽  
...  
Keyword(s):  
Uniparental Disomy ◽  
Chorionic Villus ◽  
Prenatal Testing ◽  
Chorionic Villus Sampling ◽  
Clinical Effects ◽  
Noninvasive Prenatal Testing ◽  
Genomic Imbalance ◽  
Sequencing Studies ◽  
Somatic Selection ◽  
Early Developmental

AbstractWhole chromosome uniparental disomy (UPD) has been well documented with mechanisms largely understood. However, the etiology of segmental limited UPD (segUPD) is not as clear. In a 10-year period of confirming (> 300) cases of whole chromosome UPD, we identified 86 segmental cases in both prenatal and postnatal samples. Thirty-two of these cases showed mosaic segmental UPD at 11p due to somatic selection associated with Beckwith–Wiedemann syndrome. This study focuses on apparent mechanisms associated with the remaining cases, many of which appear to represent corrections of genomic imbalance such as deletions and derivative chromosomes. In some cases, segmental UPD was associated with the generation of additional genomic imbalance while in others it apparently resulted in restoration of euploidy. Multiple tests utilizing noninvasive prenatal testing (NIPT), chorionic villus sampling (CVS) and amniotic fluid samples from the same pregnancy revealed temporal evidence of correction and a “hotspot” at 1p. Although in many cases the genomic imbalance was dosage “repaired” in the analyzed tissue, clinical effects could be sustained due to early developmental effects of the original imbalance or due to its continued existence in other tissues. In addition, if correction did not occur in the gametes there would be recurrence risks for the offspring of those individuals. Familial microarray allele patterns are presented that differentiate lack of gamete correction from somatic derived gonadal mosaicism. These results suggest that the incidence of segUPD mediated correction is underestimated and may explain the etiology of some clinical phenotypes which are undetected by routine microarray analysis and many exome sequencing studies.

scholarly journals Maternal uniparental disomy of the chromosome 14: need for growth hormone provocative tests also when a deficiency is not suspected

2019 ◽  
Vol 12 (5) ◽  
pp. e228662 ◽  
Author(s):  
Anna Tortora ◽  
Domenico La Sala ◽  
Fortunato Lonardo ◽  
Mario Vitale
Keyword(s):  
Growth Hormone ◽  
Precocious Puberty ◽  
Clinical Presentation ◽  
Marker Chromosome ◽  
Uniparental Disomy ◽  
Gnrh Analogue ◽  
Chromosome 14 ◽  
Maternal Uniparental Disomy ◽  
Temple Syndrome ◽  
One Year

Uniparental disomy (UPD) is a congenital disease characterised by the presence of two homologous chromosomes inherited from one parent in a diploid offspring. Maternal UPD of the chromosome 14 (UPD(14)mat, Temple syndrome) is a rare disorder with heterogeneous clinical presentation. Here, we report a case of UPD(14)mat with a small supernumerary marker chromosome in a 6-year-old baby girl, presenting endocrinological disorders and incomplete clinical presentation. She came to our attention because of precocious beginning of pubarche and normal stature. Most of Temple syndrome signs were lacking. Provocative tests diagnosed incomplete growth hormone (GH) response and confirmed precocious puberty. One year treatment with recombinant human GH and gonadotropin-releasing hormone (GnRH) agonists proved successful, increasing height and arresting puberty. We recommend provocative tests for GH in UPD(14)mat as a GH deficiency can be hidden by a concurrent precocious puberty. Concomitant human GH and GnRH analogue treatment can be pursued.

Co-Occurence of Reciprocal Translocation and COL2A1 Mutation in a Fetus with Severe Skeletal Dysplasia: Implications for Genetic Counseling

2015 ◽  
Vol 145 (1) ◽  
pp. 25-28 ◽  
Author(s):  
Tilman Heinrich ◽  
Indrajit Nanda ◽  
Monika Rehn ◽  
Ursula Zollner ◽  
Karen Ernestus ◽  
...  
Keyword(s):  
Genetic Counseling ◽  
Reciprocal Translocation ◽  
De Novo ◽  
Molecular Genetic ◽  
Snp Array ◽  
Chorionic Villus ◽  
Heterozygous Mutation ◽  
Chorionic Villus Sampling ◽  
Dominant Disease ◽  
Col2a1 Mutation

Achondrogenesis type II is an autosomal-dominant disease leading to severe micromelic dwarfism. Here, we report on the postmortem identification of a de novo heterozygous mutation in the COL2A1 gene (c.1529G>A, p.Gly510Asp) in a fetus who presented with generalized hydrops fetalis and severe micromelia during prenatal sonographic examinations. Initially, a reciprocal translocation t(4;17)(q31;p13) was detected in this fetus by chorionic villus sampling. Subsequent chromosomal analysis of maternal and paternal blood showed that the patient's mother was carrier of the same reciprocal translocation. SNP array analysis of the fetus did not provide evidence for chromosomal imbalances or CNVs that could be associated with the fetal phenotype. The coexistence of a cytogenetic (reciprocal translocation) and a molecular genetic (COL2A1 mutation) abnormality in the fetus carries important implications for genetic counseling.

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