PURPOSE Preimplantation genetic diagnosis (PGD) analysis can be challenging for couples who carry more than one genetic condition. In this study, we describe a new PGD strategy to select which embryo(s) to transfer for two clinically challenging cases. Both cases lack essential family members for linkage analysis including de novo mutation combined with reciprocal translocation. METHODS Diverging from conventional method, we performed direct point mutation detection, quantitative analysis of gene copy number, combined with linkage analysis assisted by SNP information from single sperm (or polar bodies), thus establishing an all-in-one protocol for single embryonic cell preimplantation diagnosis for two co-existing genetic conditions (monogenic disease and chromosomal abnormality) on the NGS-based platform. RESULTS Using this newly developed method, 15 embryos from two cases were screened, and two embryos were determined as free of the monogenic disease and specific chromosomal abnormalities created by the prospective father's reciprocal translocations. CONCLUSION This novel PGD strategy could effectively select unaffected embryo(s) for couples affected with or carrying a monogenetic disease and a reciprocal chromosome translocation concurrently.

中文翻译：

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基于单精子连锁分析的新型PGD策略，用于单基因致病变异和染色体倒易位携带者。

目的对于携带多个遗传疾病的夫妻，植入前遗传诊断（PGD）分析可能具有挑战性。在这项研究中，我们描述了一种新的PGD策略，用于为两个临床上具有挑战性的病例选择要移植的胚胎。这两个案例都缺乏必要的家庭成员进行连锁分析，包括从头突变和相互易位。方法与常规方法不同，我们进行了直接点突变检测，基因拷贝数的定量分析，并结合了单精子（或极体）的SNP信息辅助的连锁分析，从而建立了单个胚胎细胞的多合一方案基于NGS的平台上两种共存的遗传状况（单基因疾病和染色体异常）的植入前诊断。结果使用这种新开发的方法，从两个病例中筛选出15个胚胎，并确定两个胚胎不含单基因疾病和准父亲的易位产生的特定染色体异常。结论这种新颖的PGD策略可以有效地选择未受影响的胚胎，用于同时患有单基因疾病和相互染色体易位的夫妇。