Wang Wenjing, Guan Jing, Ma Minyue, Wu Xiaonan, Zhou Rui, Ji Wenkai, Dou Manman, Zhao Xiaohui, Chen Guohui, Lan Lan, Sun Jian, Gao Yuan, Peng Hongmei, Wang Qiuju
School of Medicine, Nankai University, Tianjin, 300071, China.
Senior Department of Otolaryngology Head and Neck Surgery, The 6th Medical Center of Chinese PLA General Hospital, Beijing, 100048, China.
J Assist Reprod Genet. 2025 May 19. doi: 10.1007/s10815-025-03504-7.
In order to explore the clinical effect of preimplantation genetic testing (PGT) in hereditary hearing loss (HHL), we explore the related factors affecting the pregnancy outcome of PGT of hereditary hearing loss and provide more evidence for clinical work.
From January 2015 to April 2024, we select 288 couples of child-bearing age who are at risk of conceiving children with HHL from 1444 pedigrees in Chinese Deafness Genome Project (CDGP). After genetic counseling, 19 couples elected to undergo PGT. The embryo genotypes were diagnosed by low-coverage sequencing combined with SNP linkage analysis, and followed up during pregnancy and after delivery.
The 19 couples include variants of autosomal recessive hearing loss gene GJB2, SLC26A4, USH2A, CDH23, and autosomal dominant hearing loss gene MITF, WFS1, and GSDME. The 135 embryos from the 19 couples were cultured in vitro, 93.33% (126/135) embryos got reliable genetic diagnosis, and nine embryos (6.67%) had no diagnosis. The depth of embryonic 2-3 × WGS of 205 human hearing loss genes are sufficient. Eleven women got pregnancy, and eight newborns with normal hearing have been delivered through assisted reproduction; clinical pregnancy rate was 57.89% (11/19). Pregnancy outcome is associated with the female age (P = 0.037), male age (P = 0.015), and number of transferable blastocysts obtained (P = 0.000) in per ART cycle.
PGT based on low-coverage next-generation sequencing with linkage analyses can block the transmission of deafness-related mutations to offspring. 2-3 × depth of embryo sequencing data enabled a credible testing of 205 deafness-related mutations loci. Couple age and number of retrieved oocytes are related to pregnancy outcome and can be considered prognostic indicators of PGT of HHL.
为探讨植入前基因检测（PGT）在遗传性听力损失（HHL）中的临床效果，我们探究影响遗传性听力损失PGT妊娠结局的相关因素，为临床工作提供更多依据。
2015年1月至2024年4月，我们从中国耳聋基因组计划（CDGP）的1444个家系中选取288对有生育HHL患儿风险的育龄夫妇。经过遗传咨询后，19对夫妇选择接受PGT。通过低覆盖度测序结合单核苷酸多态性（SNP）连锁分析诊断胚胎基因型，并在孕期及产后进行随访。
这19对夫妇携带常染色体隐性遗传性听力损失基因GJB2、SLC26A4、USH2A、CDH23以及常染色体显性遗传性听力损失基因MITF、WFS1和GSDME的变异。这19对夫妇的135个胚胎进行体外培养，93.33%（126/135）的胚胎获得可靠的基因诊断，9个胚胎（6.67%）未获得诊断。205个人类听力损失基因的胚胎二代全基因组测序（2-3×WGS）深度足够。11名女性成功妊娠，8名听力正常的新生儿已通过辅助生殖分娩；临床妊娠率为57.89%（11/19）。妊娠结局与每个辅助生殖周期中的女性年龄（P = 0.037）、男性年龄（P = 0.015）以及获得的可移植囊胚数量（P = 0.000）有关。
基于低覆盖度下一代测序结合连锁分析的PGT可阻断耳聋相关突变向后代的传递。胚胎测序数据达到2-3×深度能够对205个耳聋相关突变位点进行可靠检测。夫妇年龄和获卵数与妊娠结局相关，可作为HHL的PGT预后指标。
