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.

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.

Skewed X inactivation in Lesch–Nyhan disease carrier females

2017 ◽  
Vol 62 (12) ◽  
pp. 1079-1083 ◽  
Author(s):  
Rosa J Torres ◽  
Juan G Puig
Keyword(s):  
X Inactivation ◽  
Skewed X Inactivation

Skewed X Inactivation of the Normal Allele in Fully Mutated Female Carriers Determines the Levels of FMRP in Blood and the Fragile X Phenotype

2005 ◽  
Vol 9 (3) ◽  
pp. 157-162 ◽  
Author(s):  
Raquel Martínez ◽  
Victoria Bonilla-Henao ◽  
Antonio Jiménez ◽  
Miguel Lucas ◽  
Carmen Vega ◽  
...  
Keyword(s):  
Fragile X ◽  
X Inactivation ◽  
Normal Allele ◽  
Skewed X Inactivation ◽  
Female Carriers

Expression of CYP3A4 as a predictor of response to chemotherapy in peripheral T-cell lymphomas

Blood ◽  
2007 ◽  
Vol 110 (9) ◽  
pp. 3345-3351 ◽  
Author(s):  
Cristina Rodríguez-Antona ◽  
Susanna Leskelä ◽  
Magdalena Zajac ◽  
Marta Cuadros ◽  
Javier Alvés ◽  
...  
Keyword(s):  
T Cell ◽  
Clinical Response ◽  
Cell Lines ◽  
Current Therapy ◽  
Fish Analysis ◽  
Primary Tumors ◽  
Chemotherapy Drugs ◽  
T Cell Lymphomas ◽  
Response To Chemotherapy ◽  
Peripheral T Cell Lymphomas

Abstract Peripheral T-cell lymphomas (PTCLs) are aggressive tumors in which the current therapy based on multiagent chemotherapy is not successful. Since cytochrome P450 3A subfamily (CYP3A) enzymes are involved in the inactivation of chemotherapy drugs, we hypothesized that CYP3A and P-glycoprotein (MDR1) expression in these lymphomas could result in a poor clinical response. We measured tumoral CYP3A and MDR1 mRNA content in 44 T-cell lymphomas, finding a large variation in CYP3A expression. Multiplex polymerase chain reaction (PCR) analysis and fluorescence in situ hybridization (FISH) analysis showed genomic gains affecting CYP3A and MDR1 genes in T-cell lines and primary tumors, suggesting that this could be the mechanism underlying the tumoral expression variation. To test whether the tumoral expression of CYP3A and/or MDR1 could influence PTCL treatment outcome, their expression levels were compared with the clinical response and survival of the patients, finding that a high tumoral expression of CYP3A4 was significantly associated with a lower complete remission rate. This was further investigated with cell lines stably expressing CYP3A4 that exhibited an increased resistance to doxorubicin and etoposide. In conclusion, a high CYP3A4 tumoral expression could be useful to predict poor response to the standard PTCL chemotherapy; in these cases alternative chemotherapy combinations or doses should be explored.

scholarly journals Genetic Architecture of Skewed X Inactivation in the Laboratory Mouse

PLoS Genetics ◽  
2013 ◽  
Vol 9 (10) ◽  
pp. e1003853 ◽  
Author(s):  
John D. Calaway ◽  
Alan B. Lenarcic ◽  
John P. Didion ◽  
Jeremy R. Wang ◽  
Jeremy B. Searle ◽  
...  
Keyword(s):  
Genetic Architecture ◽  
Laboratory Mouse ◽  
X Inactivation ◽  
Skewed X Inactivation

scholarly journals Skewed X-inactivation is common in the general female population

2018 ◽  
Vol 27 (3) ◽  
pp. 455-465 ◽  
Author(s):  
Ekaterina Shvetsova ◽  
◽  
Alina Sofronova ◽  
Ramin Monajemi ◽  
Kristina Gagalova ◽  
...  
Keyword(s):  
X Inactivation ◽  
Female Population ◽  
Skewed X Inactivation
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