Diagnostic Cytogenetic Testing Following Positive Noninvasive Prenatal Screening Results of Sex Chromosome Abnormalities: Report of Five Cases and Systematic Review of Evidence

Overview

Journal Mol Genet Genomic Med

Specialty Genetics

Date 2020 May 9

PMID 32383339

Citations 4

Authors

Xiaolei Xie

Weihe Tan

Fuguang Li

Eric Carrano

Paola Ramirez

Autumn DiAdamo

Brittany Grommisch

Katherine Amato

Hongyan Chai

Jiadi Wen

Peining Li

Affiliations

Soon will be listed here.

Abstract

Background: Follow-up cytogenetic analysis has been recommended for cases with positive noninvasive prenatal screening (NIPS) results. This study of five cases with numerical and structural sex chromosomal abnormalities (SCA) and a review of large case series of NIPS provided guidance to improve prenatal diagnosis for SCA.

Methods: Following positive NIPS results for SCA, karyotype analysis, chromosomal microarray analysis (CMA), fluorescence in situ hybridization (FISH), and locus-specific quantitative PCR were performed on cultured amniocytes, chorionic villi cells, and stimulated lymphocytes. Review of large case series was performed to evaluate the NIPS positive rate, follow-up rate of cytogenetic analysis, positive predictive value (PPV) for major types of SCA, and relative frequencies of subtypes of major SCA.

Results: Of the five cases with positive NIPS for SCA, case 1 showed a mosaic pattern of monosomy X and isodicentric Y; case 2 showed a mosaic pattern of monosomy X confined to the placenta; cases 3 and 4 had an isochromosome of Xq, and case 5 showed a derivative chromosome 14 from a Yq/14p translocation of maternal origin. Review of literature showed that mean positive rate of NIPS for SCA was 0.61%, follow-up rate of cytogenetics analysis was 76%, and mean PPV for SCA was 48%. Mosaic patterns and structural rearrangements involving sex chromosomes were estimated in 3%-20% and 3% of SCA cases, respectively.

Conclusion: These five cases further demonstrated the necessity to pursue follow-up cytogenetic analysis to characterize mosaic patterns and structural abnormalities involving sex chromosomes and their value for prenatal genetic counseling. A workflow showing the performance of current NIPS and cytogenetic analysis for SCA was summarized. These results could facilitate an evidence-based approach to guide prenatal diagnosis of SCA.

Citing Articles

Analysis of fetal fraction in non-invasive prenatal testing with low-depth whole genome sequencing.

Xie X, Yin W, Li F, Xuan S, Ouyang Y Heliyon. 2025; 11(1):e41563.

PMID: 39850426 PMC: 11755048. DOI: 10.1016/j.heliyon.2024.e41563.

Unique Challenges of NIPT for Sex Chromosome Aneuploidy.

Wilkins-Haug L, Reimers R Clin Obstet Gynecol. 2023; 66(3):568-578.

PMID: 37650669 PMC: 10491423. DOI: 10.1097/GRF.0000000000000804.

Cell-free DNA screening positive for monosomy X: clinical evaluation and management of suspected maternal or fetal Turner syndrome.

Dowlut-McElroy T, Davis S, Howell S, Gutmark-Little I, Bamba V, Prakash S Am J Obstet Gynecol. 2022; 227(6):862-870.

PMID: 35841934 PMC: 9729468. DOI: 10.1016/j.ajog.2022.07.004.

Clinical Selection of Prenatal Diagnostic Techniques Following Positive Noninvasive Prenatal Screening Results in Southwest China.

Jing X, Liu H, Zhu Q, Liu S, Liu J, Bai T Front Genet. 2022; 12:811414.

PMID: 35154255 PMC: 8834880. DOI: 10.3389/fgene.2021.811414.

Diagnostic cytogenetic testing following positive noninvasive prenatal screening results of sex chromosome abnormalities: Report of five cases and systematic review of evidence.

Xie X, Tan W, Li F, Carrano E, Ramirez P, DiAdamo A Mol Genet Genomic Med. 2020; 8(7):e1297.

PMID: 32383339 PMC: 7336728. DOI: 10.1002/mgg3.1297.

References

Prakash S, Crenshaw M, Backeljauw P, Silberbach M, Scurlock C, Culin D . 45,X mosaicism in a population-based biobank: implications for Turner syndrome. Genet Med. 2018; 21(8):1882-1883. DOI: 10.1038/s41436-018-0411-z. View

Zhou Q, Zhu Z, Zhang B, Yu B, Cai Z, Yuan P . Clinical features and pregnancy outcomes of women with abnormal cell-free fetal DNA test results. Ann Transl Med. 2019; 7(14):317. PMC: 6694260. DOI: 10.21037/atm.2019.06.57. View

Zheng Y, Wan S, Dang Y, Song T, Chen B, Zhang J . Non-invasive prenatal testing for detection of trisomy 13, 18, 21 and sex chromosome aneuploidies in 8594 cases. Ginekol Pol. 2019; 90(5):270-273. DOI: 10.5603/GP.2019.0050. View

Al Alwan I, M K, Amir 1st , G N, A O, L B . Turner Syndrome Genotype and phenotype and their effect on presenting features and timing of Diagnosis. Int J Health Sci (Qassim). 2014; 8(2):195-202. PMC: 4166992. DOI: 10.12816/0006086. View

Hartwig T, Ambye L, Sorensen S, Jorgensen F . Discordant non-invasive prenatal testing (NIPT) - a systematic review. Prenat Diagn. 2017; 37(6):527-539. DOI: 10.1002/pd.5049. View

Lau T, Cheung S, Lo P, Pursley A, Chan M, Jiang F . Non-invasive prenatal testing for fetal chromosomal abnormalities by low-coverage whole-genome sequencing of maternal plasma DNA: review of 1982 consecutive cases in a single center. Ultrasound Obstet Gynecol. 2013; 43(3):254-64. DOI: 10.1002/uog.13277. View

Chai H, DiAdamo A, Grommisch B, Xu F, Zhou Q, Wen J . A Retrospective Analysis of 10-Year Data Assessed the Diagnostic Accuracy and Efficacy of Cytogenomic Abnormalities in Current Prenatal and Pediatric Settings. Front Genet. 2019; 10:1162. PMC: 6902283. DOI: 10.3389/fgene.2019.01162. View

Zhang B, Lu B, Yu B, Zheng F, Zhou Q, Chen Y . Noninvasive prenatal screening for fetal common sex chromosome aneuploidies from maternal blood. J Int Med Res. 2017; 45(2):621-630. PMC: 5536640. DOI: 10.1177/0300060517695008. View

Wang L, Meng Q, Tang X, Yin T, Zhang J, Yang S . Maternal mosaicism of sex chromosome causes discordant sex chromosomal aneuploidies associated with noninvasive prenatal testing. Taiwan J Obstet Gynecol. 2015; 54(5):527-31. DOI: 10.1016/j.tjog.2014.10.009. View

10.

Norton M, Jacobsson B, Swamy G, Laurent L, Ranzini A, Brar H . Cell-free DNA analysis for noninvasive examination of trisomy. N Engl J Med. 2015; 372(17):1589-97. DOI: 10.1056/NEJMoa1407349. View

11.

Liao C, Yin A, Peng C, Fu F, Yang J, Li R . Noninvasive prenatal diagnosis of common aneuploidies by semiconductor sequencing. Proc Natl Acad Sci U S A. 2014; 111(20):7415-20. PMC: 4034209. DOI: 10.1073/pnas.1321997111. View

12.

Ramdaney A, Hoskovec J, Harkenrider J, Soto E, Murphy L . Clinical experience with sex chromosome aneuploidies detected by noninvasive prenatal testing (NIPT): Accuracy and patient decision-making. Prenat Diagn. 2018; 38(11):841-848. DOI: 10.1002/pd.5339. View

13.

Li P, Pomianowski P, DiMaio M, Florio J, Rossi M, Xiang B . Genomic characterization of prenatally detected chromosomal structural abnormalities using oligonucleotide array comparative genomic hybridization. Am J Med Genet A. 2011; 155A(7):1605-15. PMC: 3745591. DOI: 10.1002/ajmg.a.34043. View

14.

McLennan A, Palma-Dias R, da Silva Costa F, Meagher S, Nisbet D, Scott F . Noninvasive prenatal testing in routine clinical practice--an audit of NIPT and combined first-trimester screening in an unselected Australian population. Aust N Z J Obstet Gynaecol. 2016; 56(1):22-8. DOI: 10.1111/ajo.12432. View

15.

Wigby K, DEpagnier C, Howell S, Reicks A, Wilson R, Cordeiro L . Expanding the phenotype of Triple X syndrome: A comparison of prenatal versus postnatal diagnosis. Am J Med Genet A. 2016; 170(11):2870-2881. PMC: 6501572. DOI: 10.1002/ajmg.a.37688. View

16.

Elsheikh M, Wass J, Conway G . Autoimmune thyroid syndrome in women with Turner's syndrome--the association with karyotype. Clin Endocrinol (Oxf). 2001; 55(2):223-6. DOI: 10.1046/j.1365-2265.2001.01296.x. View

17.

Reiss R, Discenza M, Foster J, Dobson L, Wilkins-Haug L . Sex chromosome aneuploidy detection by noninvasive prenatal testing: helpful or hazardous?. Prenat Diagn. 2017; 37(5):515-520. DOI: 10.1002/pd.5039. View

18.

Meck J, Dugan E, Matyakhina L, Aviram A, Trunca C, Pineda-Alvarez D . Noninvasive prenatal screening for aneuploidy: positive predictive values based on cytogenetic findings. Am J Obstet Gynecol. 2015; 213(2):214.e1-5. DOI: 10.1016/j.ajog.2015.04.001. View

19.

Xue Y, Zhao G, Li H, Zhang Q, Lu J, Yu B . Non-invasive prenatal testing to detect chromosome aneuploidies in 57,204 pregnancies. Mol Cytogenet. 2019; 12:29. PMC: 6584990. DOI: 10.1186/s13039-019-0441-5. View

20.

Garshasbi M, Wang Y, Hantoosh Zadeh S, Giti S, Piri S, Hekmat M . Clinical Application of Cell-Free DNA Sequencing-Based Noninvasive Prenatal Testing for Trisomies 21, 18, 13 and Sex Chromosome Aneuploidy in a Mixed-Risk Population in Iran. Fetal Diagn Ther. 2019; 47(3):220-227. DOI: 10.1159/000501014. View