AUTHOR=Zeng Yan , Gao Jiong , Yuan Hua , Zhou Lijun , Cheng Dehua , Che Ming , Qian Yandi , Fan Jiaming , Zhang Lifang , Qian Feiyan , Gao Yuling , Luo Tingting , Chen Weiping , Wang Ting , Jin Yaoxiang , Zhao Jian , Shi Xiaoliang , Li Hongmei , Pan Haitao , Xiong Cheng , Ni Yunqin , Qiu Shuchao , Zhang Tao 

TITLE=Application of FF-QuantSC for the Precise Estimation of Fetal Fraction in Non-invasive Prenatal Testing in Two SRY-Translocation Cases

JOURNAL=Frontiers in Genetics

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2020.570333

DOI=10.3389/fgene.2020.570333

ISSN=1664-8021

ABSTRACT=<p><bold>Background</bold>: Non-invasive prenatal testing (NIPT) is a commonly employed clinical method to screen for fetal aneuploidy, while the Y chromosome-based NIPT method is regarded as the gold standard for the estimation of fetal fraction (FF) of male fetuses. However, when the fetus has a derivative Y chromosome thereby containing a partial Y chromosome, the Y chromosome-based NIPT method cannot accurately calculate FF. Therefore, alternative methods to precisely calculate FF are required.</p><p><bold>Methods</bold>: Two prenatal cases could not be detected effectively using the Y chromosome-based NIPT method because of low FF. According to the Y chromosome-based method, the FF of the fetuses were 1.730 ± 0.050% (average gestation week: 18<sup>+1</sup>) and 2.307 ± 0.191% (average gestation week: 20<sup>+0</sup>) for cases 1 and 2, respectively. Using various genetic diagnostic techniques, including the BoBs™ assay, karyotype analysis, improved nucleolus-organizing region (NOR)-banding analysis, Affymetrix CytoScan 750K Array, and fluorescence <italic>in situ</italic> hybridization (FISH) analysis, we determined the genetic defects of two fetuses with translocations of the SRY locus. Further, we reassessed the FF using FF-QuantSC and X chromosome-based methods. The distribution diagram of reads for chromosome Y was also analyzed.</p><p><bold>Results</bold>: The FF of the fetuses determined by FF-QuantSC were 10.330% (gestation week: 18<sup>+4</sup>) in case 1 and 9.470% (gestation week: 21<sup>+4</sup>) in case 2, while the FF of the fetuses determined using the X chromosome-based method were 8.889% (gestation week: 18<sup>+4</sup>) in case 1 and 2.296% (gestation week: 21<sup>+4</sup>) in case 2. Both the distribution diagrams of reads for chromosome Y of the two cases showed the deletion in the long arm of the Y chromosome.</p><p><bold>Conclusion</bold>: For repeatedly low FF samples detected using the Y chromosome-based NIPT method for a long gestational week, we believe that FF-QuantSC and distribution diagrams of reads could be used as a supplement to NIPT, especially for rare cases of sex reversal caused by SRY translocation.</p>