Neumann Adina, Alcantara-Ortigoza Miguel Angel, González-Del Angel Ariadna, Zarate Díaz Nestor Alejandro, Santana Javier Sam, Porchia Leonardo M, López-Bayghen Esther
Laboratorio de Investigación y Diagnóstico Molecular, Ingenes, Mexico City 05320, Mexico.
Laboratorio de Biología Molecular, Subdirección de Investigación Médica, Instituto Nacional de Pediatría, Mexico City 04530, Mexico.
World J Clin Cases. 2021 Oct 16;9(29):8797-8803. doi: 10.12998/wjcc.v9.i29.8797.
Identifying a potential single monogenetic disorder in healthy couples is costly due to the Assisted Reproduction facilities' current methodology for screening, which focuses on the detecting multiple genetic disorders at once. Here, we report the successful application of a low-cost and fast preimplantation genetic testing for monogenic/single gene defects (PGT-M) approach for detecting propionic acidemia (PA) in embryos obtained from a confirmed heterozygous propionyl-CoA carboxylase alpha subunit () couple.
A fertile 32-years old Mexican couple with denied consanguinity sought antenatal genetic counseling. They were suspected obligate PA carriers due to a previous deceased PA male newborn with an unknown /propionyl-CoA carboxylase beta subunit () genotype. Next-Generation Sequencing revealed a heterozygous genotype for a pathogenic variant (c.2041-1G>T, ClinVar:RCV000802701.1; dbSNP:rs1367867218) in both parents. The couple requested fertilization (IVF) and PGT-M for PA. From IVF, 12 oocytes were collected and fertilized, of which two resulted in high-quality embryos. Trophectoderm biopsies and Whole Genome Amplification by a fragmentation/amplification-based method were performed and revealed that the two embryos were euploid. End-point polymerase chain reaction and further Sanger sequencing of the exon-intron borders revealed a wild-type male embryo and a heterozygous c.2041-1G>T female embryo. Both embryos were transferred, resulting in a clinical pregnancy and the delivery of a healthy male newborn (38 wk, weight: 4080 g, length: 49 cm, APGAR 9/9). The absence of PA was confirmed by expanded newborn screening.
We show that using PGT-M with Whole Genome Amplification templates, coupled with IVF, can reduce the transmission of a pathogenic variant of the gene.
由于辅助生殖机构目前的筛查方法侧重于一次性检测多种遗传疾病，因此在健康夫妇中识别潜在的单基因遗传病成本很高。在此，我们报告了一种低成本、快速的单基因/单基因缺陷植入前基因检测（PGT-M）方法在检测来自一对确诊的杂合丙酰辅酶A羧化酶α亚基（ ）夫妇的胚胎中的丙酸血症（PA）方面的成功应用。
一对32岁、有生育能力且否认近亲结婚的墨西哥夫妇寻求产前遗传咨询。由于之前有一名患丙酸血症的男婴死亡，其丙酰辅酶A羧化酶β亚基（ ）基因型未知，他们被怀疑是丙酸血症的必然携带者。下一代测序显示，父母双方均为致病性 变体（c.2041-1G>T，ClinVar:RCV000802701.1；dbSNP:rs1367867218）的杂合基因型。这对夫妇要求进行体外受精（IVF）和针对丙酸血症的PGT-M。通过IVF收集了12个卵母细胞并使其受精，其中两个发育成高质量胚胎。进行了滋养外胚层活检和基于片段化/扩增方法的全基因组扩增，结果显示这两个胚胎为整倍体。外显子-内含子边界的终点聚合酶链反应和进一步的桑格测序显示，一个是野生型 男性胚胎，另一个是杂合c.2041-1G>T女性胚胎。两个胚胎均被移植，结果临床妊娠并分娩出一名健康的男婴（38周，体重：4080克，身长：49厘米，阿氏评分9/9）。扩大的新生儿筛查证实该婴儿没有患丙酸血症。
我们表明，使用带有全基因组扩增模板的PGT-M并结合IVF，可以减少 基因致病性变体的传递。
