scholarly journals Detection of Cryptic Fragile X Full Mutation Alleles by Southern Blot in a Female and Her Foetal DNA via Chorionic Villus Sampling, Complicated by Mosaicism for 45,X0/46,XX/47,XXX

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 798
Author(s):  
Alison Pandelache ◽  
David Francis ◽  
Ralph Oertel ◽  
Rebecca Dickson ◽  
Rani Sachdev ◽  
...  
Keyword(s):  
Southern Blot ◽  
Fragile X ◽  
Chorionic Villus ◽  
Prenatal Testing ◽  
Chorionic Villus Sampling ◽  
Full Mutation ◽  
Fmr1 Premutation ◽  
Full Mutation Allele ◽  
History Of ◽  
Polymerase Chain

We describe a female with a 72 CGG FMR1 premutation (PM) (CGG 55–199) and family history of fragile X syndrome (FXS), referred for prenatal testing. The proband had a high risk of having an affected pregnancy with a full mutation allele (FM) (CGG > 200), that causes FXS through hypermethylation of the FMR1 promoter. The CGG sizing analysis in this study used AmplideX triplet repeat primed polymerase chain reaction (TP-PCR) and long-range methylation sensitive PCR (mPCR). These methods detected a 73 CGG PM allele in the proband’s blood, and a 164 CGG PM allele in her male cultured chorionic villus sample (CVS). In contrast, the Southern blot analysis showed mosaicism for: (i) a PM (71 CGG) and an FM (285–768 CGG) in the proband’s blood, and (ii) a PM (165 CGG) and an FM (408–625 CGG) in the male CVS. The FMR1 methylation analysis, using an EpiTYPER system in the proband, showed levels in the range observed for mosaic Turner syndrome. This was confirmed by molecular and cytogenetic karyotyping, identifying 45,X0/46,XX/47,XXX lines. In conclusion, this case highlights the importance of Southern blot in pre- and postnatal testing for presence of an FM, which was not detected using AmplideX TP-PCR or mPCR in the proband and her CVS.

scholarly journals Gene Expression in First Trimester Preeclampsia Placenta

2010 ◽  
Vol 13 (2) ◽  
pp. 134-139 ◽  
Author(s):  
Sandra A. Founds ◽  
Lauren A. Terhorst ◽  
Kirk P. Conrad ◽  
W. Allen Hogge ◽  
Arun Jeyabalan ◽  
...  
Keyword(s):  
Candidate Genes ◽  
Chorionic Villus ◽  
First Trimester ◽  
Chorionic Villus Sampling ◽  
Qrt Pcr ◽  
Individualized Care ◽  
Additional Control ◽  
Polymerase Chain ◽  
The Difference

Background. The goal of this study was to further validate eight candidate genes identified in a microarray analysis of first trimester placentas in preeclampsia. Material and method. Surplus chorionic villus sampling (CVS) specimens of 4 women subsequently diagnosed with preeclampsia (PE) and 8 control women (C) without preeclampsia analyzed previously by microarray and 24 independent additional control samples (AS) were submitted for confirmatory studies by quantitative real-time polymerase chain reaction (qRT-PCR). Results. Downregulation was significant in FSTL3 in PE as compared to C and AS (p = .04). PAEP was downregulated, but the difference was only significant between C and AS (p = .002) rather than between PE and either of the control groups. Expression levels for CFH, EPAS1, IGFBP1, MMP12, and SEMA3C were not statistically different among groups, but trends were consistent with microarray results; there was no anti-correlation. S100A8 was not measurable in all samples, probably because different probes and primers were needed. Conclusions. This study corroborates reduced FSTL3 expression in the first trimester of preeclampsia. Nonsignificant trends in the other genes may require follow-up in studies powered for medium or medium/large effect sizes. qRT-PCR verification of the prior microarray of CVS may support the placental origins of preeclampsia hypothesis. Replication is needed for the candidate genes as potential biomarkers of susceptibility, early detection, and/or individualized care of maternal—infant preeclampsia.

Invasive Prenatal Diagnosis

2020 ◽  
Author(s):  
Kimberly Zayhowski
Keyword(s):  
Genetic Counseling ◽  
Prenatal Diagnosis ◽  
Genetic Testing ◽  
Prenatal Care ◽  
Chorionic Villus ◽  
Prenatal Testing ◽  
Chorionic Villus Sampling ◽  
Genetic Tests ◽  
Genetic Technologies ◽  
Invasive Techniques

Despite recent advances in genetic technologies that are making invasive prenatal diagnosis less common, amniocentesis and chorionic villus sampling (CVS) remain an integral part of prenatal care. A multitude of tests, including a variety of genetic tests, can be performed using samples collected from either procedure. Although invasive testing has limitations, many genetic conditions can only be diagnosed through invasive techniques during pregnancy. Invasive testing continues to assist patients and providers in making informed decisions regarding the care of pregnancies. This review details amniocentesis and chorionic villus sampling with a focus on genetic testing, describing why the tests are performed, the way in which they are performed, and the associated limitations and complications of the procedures.  This review 5 figures, 3 tables, and 26 references. Keywords: prenatal diagnosis, amniocentesis, chorionic villus sampling, genetic testing, genetic counseling, invasive prenatal testing, pregnancy, aneuploidy

Uptake of Noninvasive Prenatal Testing in Chinese Women following Positive Down Syndrome Screening

2014 ◽  
Vol 37 (2) ◽  
pp. 141-147 ◽  
Author(s):  
C.F. Poon ◽  
W.C. Tse ◽  
K.O. Kou ◽  
K.Y. Leung
Keyword(s):  
Down Syndrome ◽  
Chinese Women ◽  
Multivariable Analysis ◽  
Chorionic Villus ◽  
Prenatal Testing ◽  
First Trimester ◽  
Screening Methods ◽  
Chorionic Villus Sampling ◽  
Noninvasive Prenatal Testing ◽  
Down Syndrome Screening

Objectives: To investigate how the introduction of noninvasive prenatal testing (NIPT) influenced women's testing choices following a positive Down syndrome screening. Methods: A retrospective study was conducted to compare differences in the uptake rates of invasive prenatal diagnosis (IPD) or no testing in one public hospital 1 year before (pre-NIPT) and 1 and 2 years after the introduction of NIPT in private in August 2011 using descriptive analysis and a χ2 test. Conventional screening was funded publicly, but NIPT was not. Multivariable binary logistic regression was used to determine factors affecting choices. Results: In pre-NIPT and in years 1 and 2 after the introduction of NIPT, 306, 362 and 401 women who screened positive were seen, respectively. In year 1 and year 2, 12.6 and 26.7% of them underwent NIPT while IPD was decreased by 16.3 and 25.6%, respectively (p < 0.001). Both chorionic villus sampling and amniocentesis decreased in year 1, but only the former in year 2. However, the rate of declining further testing was similar before and after NIPT (p = 0.213). In multivariable analysis, first trimester screening, nulliparity and working women were significant predictors of accepting NIPT, while only nulliparity was a predictor of declining IPD (OR = 0.61). Conclusions: Introduction of NIPT resulted in a significant decrease in IPD for 2 consecutive years.

Trends in Invasive Prenatal Diagnosis: Effect of Sequential Screening and Noninvasive Prenatal Testing

2015 ◽  
Vol 39 (4) ◽  
pp. 292-296 ◽  
Author(s):  
Adeeb Khalifeh ◽  
Stuart Weiner ◽  
Vincenzo Berghella ◽  
Alan Donnenfeld
Keyword(s):  
Prenatal Diagnosis ◽  
Chorionic Villus ◽  
Prenatal Testing ◽  
Chorionic Villus Sampling ◽  
Invasive Procedures ◽  
Noninvasive Prenatal Testing ◽  
Sequential Screening ◽  
Period 2 ◽  
Prenatal Diagnostic ◽  
The Impact

Objective: To examine trends in the incidence and method of invasive prenatal diagnosis due to the impact of sequential screening and noninvasive prenatal testing. Methods: This is a retrospective review of all pregnancies that have undergone invasive prenatal diagnostic testing between June 2002 and June 2014, divided in 3 periods: period 1 from June 2002 to October 2006, period 2 from November 2006 to December 2011, and period 3 from January 2012 to June 2014. The main outcome measures were trends in the incidence and method of each procedure. Results: There were 88,135 deliveries and 6,080 invasive procedures during the study period. In period 1, 2,755 (8.8%) procedures were carried out, in period 2 2,820 (7.3%), and in period 3 505 (2.5%; p < 0.01). In period 1, there were 1,990 (6.3%) cases of amniocentesis, 1,646 (4.3%) in period 2, and 254 (1.2%) in period 3 (p < 0.01). In addition, in 765 (2.5%) cases, chorionic villus sampling (CVS) was performed in period 1, compared to 1,174 (3.0%) cases in period 2 and 251 (1.3%) cases in period 3 (p < 0.01). Advanced maternal age as the sole indication for invasive procedures decreased significantly over time, while the indication of abnormal serum screening and abnormal ultrasound findings increased (p < 0.01). Conclusion: There was a significant decline in the incidence of invasive prenatal testing over the 12 years of the study. The decrease in amniocentesis was more marked than that in CVS.

A Novel Polymorphism in the FMR1 Gene: Implications for Clinical Testing of Fragile X Syndrome

2008 ◽  
Vol 132 (1) ◽  
pp. 95-98
Author(s):  
Bharat Thyagarajan ◽  
Matthew Bower ◽  
Michael Berger ◽  
Sidney Jones ◽  
Michelle Dolan ◽  
...  
Keyword(s):  
Polymerase Chain Reaction ◽  
Mental Retardation ◽  
Fragile X Syndrome ◽  
Southern Blot ◽  
Trinucleotide Repeat ◽  
Fragile X ◽  
Fmr1 Gene ◽  
Chain Reaction ◽  
Cgg Repeat ◽  
Polymerase Chain

Abstract Fragile X syndrome is the most common cause of inherited mental retardation among males. In most cases, the molecular basis of fragile X syndrome is the expansion and subsequent methylation of a CGG trinucleotide repeat in the 5′ untranslated region of the fragile X mental retardation 1 (FMR1) gene. Laboratory diagnosis usually relies on a combination of Southern blot and polymerase chain reaction analyses. In this case report we describe an unusual Southern blot result in a patient who presented with developmental delay and had a normal CGG repeat number by polymerase chain reaction analysis. Further investigation revealed a novel G3310C transversion in the FMR1 gene resulting in a new recognition site for the BssHII restriction enzyme. This novel restriction site could potentially mimic a partial deletion of the FMR1 gene on Southern blot analysis and thus represents a possible pitfall in the diagnosis of fragile X syndrome.

scholarly journals Comparison Between the Polymerase Chain Reaction-Based Screening and the Southern Blot Methods for Identification of Fragile X Syndrome

2012 ◽  
Vol 16 (11) ◽  
pp. 1303-1308 ◽  
Author(s):  
Karen M. Carvalho Curtis-Cioffi ◽  
Debora Aparecida Rodrigueiro ◽  
Valter Curi Rodrigues ◽  
Regina M. Barretto Cicarelli ◽  
Raquel Mantuaneli Scarel-Caminaga
Keyword(s):  
Polymerase Chain Reaction ◽  
Fragile X Syndrome ◽  
Southern Blot ◽  
Fragile X ◽  
Chain Reaction ◽  
Polymerase Chain
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