Neurofibroma type 1 (NFI) is an autosomal dominant genetic disease associated with cancer and cognitive dysfunction. The 50% de novo mutation rate and numerous mutation types of the NF1 gene pose challenges to preimplantation genetic testing (PGT) for NFI. In 2020, a couple was subjected to next-generation sequencing (NGS)-based PGT at our center. Both husband and wife carried de novo NF1 mutations. Biopsied trophectoderm samples underwent whole-genome amplification using multiple displacement amplification. NGS was conducted to detect NF1 mutations as well as 105 closely linked single-nucleotide polymorphisms (SNPs) flanking NF1. Since no affected family member was available, the affected embryos identified by NF1-targeted sequencing were assigned as probands, based on which a haplotype analysis was constructed with informative SNP sites. Sanger sequencing was administrated for verification. Aneuploidy screening through NGS was performed in the same PGT cycle. Finally, among the nine biopsied blastocysts, two unaffected and euploid blastocysts were obtained in the couple, and one of the blastocysts was transferred in a frozen–thawed embryo transfer (FET) cycle. The outcome of FET is under observation. This study is the first to apply NGS-based PGT for NFI. In cases of sporadic NFI cases without affected family members, NGS-SNP can perform haploid analysis in an accurate manner by assigning the affected embryos as probands.

1型神经纤维瘤（NFI）是与癌症和认知功能障碍相关的常染色体显性遗传疾病。从头突变率50％和NF1基因的众多突变类型对NFI的植入前基因测试（PGT）提出了挑战。2020年，一对夫妇在我们中心接受了基于下一代测序（NGS）的PGT。丈夫和妻子均携带新的NF1突变。活检的滋养外胚层样品使用多重置换扩增进行了全基因组扩增。进行了NGS检测NF1突变以及NF1侧翼的105个紧密相连的单核苷酸多态性（SNP）。由于没有受影响的家庭成员，因此NF1鉴定出受影响的胚胎靶向测序被指定为先证者，在此基础上构建具有信息性SNP位点的单倍型分析。管理Sanger测序以进行验证。在同一PGT循环中通过NGS进行非整倍性筛选。最终，在这9个活检胚泡中，这对夫妇获得了两个未受影响的和整倍体胚泡，其中一个胚泡以冷冻融化的胚胎移植（FET）周期进行了移植。FET的结果正在观察中。这项研究是第一个将基于NGS的PGT用于NFI的研究。在没有受影响家庭成员的零星NFI病例中，NGS-SNP可以通过将受影响的胚胎指定为先证者来准确地进行单倍体分析。