Medical School of Chinese PLA General Hospital, Beijing, China.
Department of Pediatrics, The First Medical Center of Chinese PLA General Hospital, Beijing, China.
Mol Genet Genomic Med. 2022 Jul;10(7):e1952. doi: 10.1002/mgg3.1952. Epub 2022 Apr 16.
Noninvasive prenatal diagnosis (NIPD) based on cell-free DNA (cfDNA) has been introduced into the clinical application for some monogenic disorders but not for tuberous sclerosis (TSC) yet, which is an autosomal dominant disease caused by various variations in TSC1 or TSC2 gene. We aimed to explore the feasibility of NIPD on TSC.
We recruited singleton pregnancies at risk of TSC from 14 families with a proband child. Definitive NIPD for TSC was performed using targeted next-generation sequencing of cfDNA in parallel with maternal white blood cell DNA (wbcDNA). The NIPD results were validated by amniocentesis or postnatal gene testing and follow-up of the born children.
Missense mutations, nonsense mutations, frameshift mutations, and splice-site variants which were obtained through de-novo, maternal, or paternal inheritance were included. The mean and minimum gestational weeks of NIPD were 17.18 ± 5.83 and 8 weeks, respectively. The NIPD results were 100% consistent with the amniocentesis or postnatal gene testing and follow-up of the born children.
This study demonstrates that NIPD based on cfDNA is feasible for TSC, but required to be confirmed with more samples. Studies on TSC can contribute to the application and promotion of NIPD for monogenic disorders.
基于游离胎儿 DNA（cfDNA）的无创性产前诊断（NIPD）已被引入某些单基因疾病的临床应用，但尚未用于结节性硬化症（TSC），这是一种由 TSC1 或 TSC2 基因突变引起的常染色体显性疾病。我们旨在探讨 NIPD 在 TSC 中的应用可行性。
我们从 14 个先证者患儿的家庭中招募了患有 TSC 风险的单胎妊娠。使用 cfDNA 的靶向下一代测序并行母体白细胞 DNA（wbcDNA）对 TSC 进行明确的 NIPD。通过羊膜穿刺术或产后基因检测和出生后儿童的随访来验证 NIPD 结果。
包括新获得的、母源性或父源性遗传的错义突变、无义突变、移码突变和剪接位点变异。NIPD 的平均和最小孕周分别为 17.18±5.83 和 8 周。NIPD 结果与羊膜穿刺术或产后基因检测和出生后儿童的随访结果完全一致。
本研究表明，基于 cfDNA 的 NIPD 可用于 TSC，但需要更多样本进行验证。对 TSC 的研究有助于推动 NIPD 在单基因疾病中的应用。
