Confirmation of prenatal diagnosis of sex chromosome mosaicism

Abstract Objective To analyze the karyotype of sex chromosome mosaicism in our prenatal diagnosis of 14034 pregnant women in their second trimester, and report the rate of sex chromosome mosaicism and their clinical outcomes.Methods A retrospective analysis of cytogenetic studies of 14043 cases of pregnant women from the Genetic Counseling Clinic from May 2017 to January 2020 by amniocentesis, were performed. Results A total of 46 cases of sex chromosome mosaicism were found, and the sex chromosome mosaicism rate was 0.328%, mainly including four types of mosaicism: mos45,X/46,XX(12); mos45,X/46,XY (11); mos47XXX(or XXY or XYY)/46XX(or XY)(11); and other types of complex abnormal karyotype mosaic(12). Among the 46 fetuses with sex chromosome mosaicism, the indications of prenatal diagnosis includes the numerical abnormality of sex chromosome by NIPT(23/46)，the high risk of trisomy 21 by serum screening(12/46)，abnomal ultrosound(4/46), the advanced maternal age(age ≥35)(4/46), and the histories of abnormal pregnancy(3/46). According to the results of cytogenetic analysis and genetic counseling, the pregnant women would decide to continue or terminate their pregnancy. Conclusion Prenatal cytogenetic diagnosis by amniocentesis is an accurate and convenient method and helps to avoid the delivery of fetuses with chromosomal diseases and reduce the risk of fetal malformation.

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Prenatal diagnosis of sex chromosome mosaicism with two marker chromosomes in three cell lines and a review of the literature

Molecular Medicine Reports ◽

10.3892/mmr.2018.9798 ◽

2018 ◽

Cited By ~ 1

Author(s):

Jianli Zheng ◽

Xiaoyu Yang ◽

Haiyan Lu ◽

Yongjuan Guan ◽

Fangfang Yang ◽

...

Keyword(s):

Prenatal Diagnosis ◽

Cell Lines ◽

Sex Chromosome ◽

Review Of The Literature ◽

Chromosome Mosaicism ◽

Marker Chromosomes

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Integrated CNV-seq, karyotyping and SNP-array analyses for effective prenatal diagnosis of chromosomal mosaicism

BMC Medical Genomics ◽

10.1186/s12920-021-00899-x ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Na Ma ◽

Hui Xi ◽

Jing Chen ◽

Ying Peng ◽

Zhengjun Jia ◽

...

Keyword(s):

Prenatal Diagnosis ◽

Sex Chromosome ◽

Snp Array ◽

Genomic Rearrangements ◽

Chromosomal Mosaicism ◽

Chromosomal Microarray ◽

Chromosomal Microarray Analysis ◽

Low Level ◽

Autosomal Aneuploidy ◽

Number Variation

Abstract Background Emerging studies suggest that low‐coverage massively parallel copy number variation sequencing (CNV-seq) more sensitive than chromosomal microarray analysis (CMA) for detecting low-level mosaicism. However, a retrospective back-to-back comparison evaluating accuracy, efficacy, and incremental yield of CNV-seq compared with CMA is warranted. Methods A total of 72 mosaicism cases identified by karyotyping or CMA were recruited to the study. There were 67 mosaic samples co-analysed by CMA and CNV-seq, comprising 40 with sex chromosome aneuploidy, 22 with autosomal aneuploidy and 5 with large cryptic genomic rearrangements. Results Of the 67 positive mosaic cases, the levels of mosaicism defined by CNV-seq ranged from 6 to 92% compared to the ratio from 3 to 90% by karyotyping and 20% to 72% by CMA. CNV-seq not only identified all 43 chromosomal aneuploidies or large cryptic genomic rearrangements detected by CMA, but also provided a 34.88% (15/43) increased yield compared with CMA. The improved yield of mosaicism detection by CNV-seq was largely due to the ability to detect low level mosaicism below 20%. Conclusion In the context of prenatal diagnosis, CNV-seq identified additional and clinically significant mosaicism with enhanced resolution and increased sensitivity. This study provides strong evidence for applying CNV-seq as an alternative to CMA for detection of aneuploidy and mosaic variants.

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Noninvasive prenatal detection of fetal sex chromosome abnormalities using the semiconductor sequencing platform (SSP) in Southern China

Journal of Assisted Reproduction and Genetics ◽

10.1007/s10815-020-02056-2 ◽

2021 ◽

Vol 38 (3) ◽

pp. 727-734

Author(s):

Jiexia Yang ◽

Yaping Hou ◽

Fangfang Guo ◽

Haishan Peng ◽

Dongmei Wang ◽

...

Keyword(s):

Prenatal Diagnosis ◽

High Risk ◽

Sex Chromosome ◽

Southern China ◽

Prenatal Testing ◽

Clinical Genetic ◽

Fetal Sex ◽

Sequencing Platform ◽

Cell Free Fetal Dna ◽

Fetal Aneuploidies

Abstract Background Noninvasive prenatal testing (NIPT) has been widely used to screen for fetal aneuploidies, including fetal sex chromosome aneuploidies (SCAs). However, there is less information on the performance of NIPT in detecting SCAs. Methods A cohort of 47,800 pregnancies was recruited to review the high-risk NIPT results for SCAs. Cell-free fetal DNA (cffDNA) was extracted and sequenced. All NIPT high-risk cases were recommended to undergo invasive prenatal diagnosis for karyotyping analysis and chromosome microarray analysis (CMA). Results A total of 238 high-risk cases were detected by NIPT, including 137 cases of 45,X, 27 cases of 47,XXX, and 74 cases of 47,XYY/47,XXY. Prenatal diagnosis, including karyotyping analysis and CMA, was available in 170 cases. The positive predictive value (PPV) was 30.00% for 45,X, 70.58% for 47,XXX, and 81.13% for 47,XYY/47,XXY. In addition, 13 cases of sex chromosome mosaicism and 9 cases of sex chromosome CNVs were incidentally found in this study. Conclusion Our study showed that NIPT was reliable for screening SCAs based on a large sample, and it performed better in predicting sex chromosome trisomies than monosomy X. Our study will provide an important reference for clinical genetic counseling and further processing of the results.

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Fluorescence In Situ Hybridization Analysis of Sex-Chromosome Mosaicism in Azoospermic Men

Journal of Andrology ◽

10.1002/j.1939-4640.2001.tb03437.x ◽

2001 ◽

Vol 22 (6) ◽

pp. 970-972 ◽

Cited By ~ 8

Author(s):

HIROSHI OKADA ◽

MASAKI DOBASHI ◽

TAKAFUMI YAMAZAKI ◽

MASATO FUJISAWA ◽

SOICHI ARAKAWA ◽

...

Keyword(s):

In Situ Hybridization ◽

Fluorescence In Situ Hybridization ◽

Sex Chromosome ◽

Hybridization Analysis ◽

Chromosome Mosaicism

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Rapid and simple prenatal diagnosis of common chromosome disorders: advantages and disadvantages of the molecular methods FISH and QF-PCR

Reproduction ◽

10.1530/rep.0.1260279 ◽

2003 ◽

pp. 279-297 ◽

Cited By ~ 80

Author(s):

MA Hulten ◽

S Dhanjal ◽

B Pertl

Keyword(s):

Prenatal Diagnosis ◽

Sex Chromosome ◽

Chromosome Analysis ◽

Maternal Serum ◽

Molecular Techniques ◽

Maternal Serum Screening ◽

Advantages And Disadvantages ◽

Microscopy Analysis ◽

Chromosome Disorder

Molecular techniques have been developed for prenatal diagnosis of the most common chromosome disorders (trisomies 21, 13, 18 and sex chromosome aneuploidies) where results are available within a day or two. This involves fluorescence in situ hybridization (FISH) and microscopy analysis of fetal cells or quantitative fluorescence polymerase chain reaction (QF-PCR) on fetal DNA. Guidance is provided on the technological pitfalls in setting up and running these methods. Both methods are reliable, and the risk for misdiagnosis is low, although slightly higher for FISH. FISH is also more labour intensive than QF-PCR, the latter lending itself more easily to automation. These tests have been used as a preamble to full chromosome analysis by microscopy. However, there is a trend to apply the tests as 'stand-alone' tests for women who are at relatively low risk of having a baby with a chromosome disorder, in particular that associated with advanced age or results of maternal serum screening programmes. These women comprise the majority of those currently offered prenatal diagnosis with respect to fetal chromosome disorders and if introduced on a larger scale, the use of FISH and QF-PCR would lead to substantial economical savings. The implication, on the other hand, is that around one in 500 to one in 1000 cases with a mentally and/or physically disabling chromosome disorder would remain undiagnosed.

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