Jeppesen Line Dahl, Hatt Lotte, Singh Ripudaman, Schelde Palle, Ravn Katarina, Toft Christian Liebst, Laursen Maria Bach, Hedegaard Jakob, Christensen Inga Baasch, Nicolaisen Bolette Hestbek, Andreasen Lotte, Pedersen Lars Henning, Vogel Ida, Lildballe Dorte Launholt
ARCEDI Biotech, Vejle, Denmark.
Center for Fetal Diagnostics, Aarhus University, Aarhus, Denmark.
Front Genet. 2023 Sep 27;14:1188472. doi: 10.3389/fgene.2023.1188472. eCollection 2023.
Circulating fetal cells isolated from maternal blood can be used for prenatal testing, representing a safe alternative to invasive testing. The present study investigated the potential of cell-based noninvasive prenatal testing (NIPT) for diagnosing monogenic disorders dependent on the mode of inheritance. Maternal blood samples were collected from women opting for prenatal diagnostics for specific monogenic disorders ( = 7). Fetal trophoblasts were enriched and stained using magnetic activated cell sorting and isolated by fluorescens activated single-cell sorting. Individual cells were subject to whole genome amplification, and cells of fetal origin were identified by DNA-profiling using short tandem repeat markers. The amplified fetal DNA was input for genetic testing for autosomal dominant-, autosomal recessive-, X-linked and repeat expansion disorders by direct variant analysis and haplotyping. The cell-based NIPT results were compared with those of invasive testing. In two cases at risk of skeletal dysplasia, caused by variants in the gene (autosomal dominant disorders), cell-based NIPT correctly stated an affected fetus, but allelic dropout of the normal alleles were observed in both cases. Cell-based NIPT gave an accurate result in two cases at risk of autosomal recessive disorders, where the parents carried either different diastrophic dysplasia causing variants in the gene or the same cystic fibrosis disease-causing variant in the gene. Cell-based NIPT accurately identified an affected male fetus in a pregnancy at risk of Duchenne muscular dystrophy ( gene, X-linked recessive disorders). In two cases at risk of the myotonic dystrophy type 1 ( gene, repeat expansion disorder), cell-based NIPT correctly detected an affected and an unaffected fetus, respectively. Circulating fetal cells can be used to detect both maternally- and paternally inherited monogenic disorders irrespective of the type of variant, however, the risk of allelic dropout must be considered. We conclude that the clinical interpretation of the cell-based NIPT result thus varies depending on the disorders' mode of inheritance.
从母体血液中分离出的循环胎儿细胞可用于产前检测，是侵入性检测的一种安全替代方法。本研究调查了基于细胞的非侵入性产前检测（NIPT）在诊断取决于遗传方式的单基因疾病方面的潜力。从选择针对特定单基因疾病进行产前诊断的女性中采集母体血样（n = 7）。使用磁珠分选法富集和染色胎儿滋养层细胞，并通过荧光激活单细胞分选法进行分离。对单个细胞进行全基因组扩增，并使用短串联重复序列标记通过DNA分析鉴定胎儿来源的细胞。将扩增的胎儿DNA输入进行常染色体显性、常染色体隐性、X连锁和重复扩增疾病的基因检测，采用直接变异分析和单倍型分析。将基于细胞的NIPT结果与侵入性检测结果进行比较。在两例因 基因变异（常染色体显性疾病）而有骨骼发育不良风险的病例中，基于细胞的NIPT正确判定胎儿患病，但两例均观察到正常等位基因的等位基因脱失。在两例有常染色体隐性疾病风险的病例中，基于细胞的NIPT给出了准确结果，其中父母携带不同的导致 基因中不同的脊柱发育不良变异或相同的导致 基因中囊性纤维化疾病的变异。基于细胞的NIPT在一例有杜氏肌营养不良风险（ 基因，X连锁隐性疾病）的妊娠中准确鉴定出患病男性胎儿。在两例有1型强直性肌营养不良风险（ 基因，重复扩增疾病）的病例中，基于细胞的NIPT分别正确检测出患病胎儿和未患病胎儿。循环胎儿细胞可用于检测母系和父系遗传的单基因疾病，无论变异类型如何，然而，必须考虑等位基因脱失的风险。我们得出结论，基于细胞的NIPT结果的临床解释因此因疾病的遗传方式而异。
