Li Xiaoli, Huang Qiuxiang, Zhong Fuchun, Liu Yun, Chen Zhibiao, Lin Juan, Fan Zhongli, Lan Fenghua, Wang Zhihong
Department of Clinical Laboratory Medicine, Dongfang Hospital of Xiamen University, School of Medicine, Xiamen University, Fuzhou, Fujian, China.
Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Dongfang Hospital of Xiamen University, School of Medicine, Xiamen University, Fuzhou, Fujian, China.
J Hum Genet. 2025 Feb;70(2):113-119. doi: 10.1038/s10038-024-01307-9. Epub 2024 Nov 25.
In this study, we aimed to apply preimplantation genetic testing for monogenic disorders (PGT-M) based on mutated allele revealed by sequencing with aneuploidy and linkage analyses (MARSALA) to block the transmission of inborn errors of metabolism (IEMs). After the disease-causing variants were identified through genetic testing, four carrier couples having children affected with IEMs, including methylmalonic aciduria, glutaric acidemia type 1, beta-ketothiolase deficiency, and ornithine transcarbamylase deficiency, sought PGT-M. A series of PGT procedures involving intracytoplasmic sperm injection, blastocyst culture, biopsy of trophectoderm cells, and next-generation sequencing (NGS)-based MARSALA, was performed to provide comprehensive chromosome screening and variant gene analysis. Finally, embryos were selected for transfer, and prenatal diagnosis was conducted to confirm the PGT-M results. All four carrier couples obtained transferrable embryos after PGT. The results of the prenatal diagnosis were consistent with the PGT results, and all couples gave birth to healthy babies free of IEMs. The results of this study confirm that NGS-based MARSALA is an effective approach for families with IEMs to prevent the subsequent transmission of pathological genetic variants to the next generation.
在本研究中，我们旨在应用基于测序及非整倍体和连锁分析揭示的突变等位基因的单基因疾病植入前基因检测（PGT-M）来阻断先天性代谢缺陷（IEMs）的传递。通过基因检测确定致病变异后，四对有受IEMs影响子女的携带者夫妇，包括甲基丙二酸血症、1型戊二酸血症、β-酮硫解酶缺乏症和鸟氨酸转氨甲酰酶缺乏症患者，寻求PGT-M。进行了一系列PGT程序，包括胞浆内单精子注射、囊胚培养、滋养外胚层细胞活检以及基于下一代测序（NGS）的MARSALA，以提供全面的染色体筛查和变异基因分析。最后，选择胚胎进行移植，并进行产前诊断以确认PGT-M结果。所有四对携带者夫妇在PGT后均获得了可移植胚胎。产前诊断结果与PGT结果一致，所有夫妇均生下了无IEMs的健康婴儿。本研究结果证实，基于NGS的MARSALA是IEMs家庭预防病理性遗传变异向下一代传递的有效方法。
