Background: 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.

Methods: 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⁺¹) and 2.307 ± 0.191% (average gestation week: 20⁺⁰) 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 in situ 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.

Results: The FF of the fetuses determined by FF-QuantSC were 10.330% (gestation week: 18⁺⁴) in case 1 and 9.470% (gestation week: 21⁺⁴) in case 2, while the FF of the fetuses determined using the X chromosome-based method were 8.889% (gestation week: 18⁺⁴) in case 1 and 2.296% (gestation week: 21⁺⁴) 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.

Conclusion: 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.

背景：非侵入性产前检查（NIPT）是筛查胎儿非整倍性的常用临床方法，而基于Y染色体的NIPT方法被视为评估男性胎儿胎儿分数（FF）的金标准。但是，当胎儿具有衍生的Y染色体从而包含部分Y染色体时，基于Y染色体的NIPT方法无法准确计算FF。因此，需要其他方法来精确计算FF。

方法：由于FF低，无法使用基于Y染色体的NIPT方法有效地检测出两个产前病例。根据基于Y染色体的方法，案例1和案例2的胎儿FF分别为1.730±0.050％（平均妊娠周：18 ⁺¹）和2.307±0.191％（平均妊娠周：20 ⁺⁰）。使用各种遗传诊断技术，包括BoBs™分析，核型分析，改进的核仁组织区（NOR）带分析，Affymetrix CytoScan 750K阵列和荧光原位杂交（FISH）分析，我们确定了SRY基因座易位的两个胎儿的遗传缺陷。此外，我们使用FF-QuantSC和基于X染色体的方法重新评估了FF。还分析了Y染色体读段的分布图。

结果：通过FF-QuantSC测定的胎儿的FF在情况1下为10.330％（妊娠周：18 ⁺⁴），在情况2下为9.470％（妊娠周：21 ⁺⁴），而使用X来确定的胎儿FF基于染色体的方法在案例1中为8.889％（妊娠周：18 ⁺⁴），在案例2中为2.296％（妊娠周：21 ⁺⁴）。两个案例中Y染色体读数的分布图均显示缺失。 Y染色体的长臂。

结论：对于长期孕周使用基于Y染色体的NIPT方法反复检测到的低FF样品，我们认为FF-QuantSC和读数分布图可作为NIPT的补充，特别是对于由以下原因引起的性逆转的罕见情况SRY易位。