基于低覆盖率下一代测序与连锁分析的植入前基因检测在遗传性听力损失家族中的临床应用。

IF 3.2 3区 医学 Q2 GENETICS & HEREDITY
Wenjing Wang, Jing Guan, Minyue Ma, Xiaonan Wu, Rui Zhou, Wenkai Ji, Manman Dou, Xiaohui Zhao, Guohui Chen, Lan Lan, Jian Sun, Yuan Gao, Hongmei Peng, Qiuju Wang
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引用次数: 0

摘要

目的:探讨胚胎植入前基因检测(PGT)在遗传性听力损失(HHL)患者中的临床效果,探讨影响遗传性听力损失患者PGT妊娠结局的相关因素,为临床工作提供更多依据。方法:2015年1月至2024年4月,从中国耳聋基因组计划(CDGP)的1444个家系中,选择288对育龄且有生育HHL风险的夫妇。经过遗传咨询,19对夫妇选择接受PGT。采用低覆盖率测序结合SNP连锁分析诊断胚胎基因型,并在妊娠期间和分娩后随访。结果:19对夫妇包括常染色体隐性听力损失基因GJB2、SLC26A4、USH2A、CDH23变异,以及常染色体显性听力损失基因MITF、WFS1和GSDME变异。对19对夫妇的135个胚胎进行体外培养,93.33%(126/135)胚胎得到可靠的遗传诊断,9个胚胎(6.67%)未得到诊断。205个人听力损失基因的胚胎2 ~ 3 × WGS深度充足。11名妇女怀孕,8名听力正常的新生儿通过辅助生殖出生;临床妊娠率为57.89%(11/19)。妊娠结局与女性年龄(P = 0.037)、男性年龄(P = 0.015)和每个ART周期获得的可转移囊胚数量(P = 0.000)相关。结论:基于低覆盖率下一代测序和连锁分析的PGT可以阻断耳聋相关突变向后代的传递。2-3倍深度的胚胎测序数据能够可靠地检测205个耳聋相关突变位点。夫妻年龄和取卵数量与妊娠结局有关,可作为HHL PGT的预后指标。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Clinical application of preimplantation genetic testing based on low-coverage next-generation sequencing with linkage analyses in hereditary hearing loss families.

Purpose: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

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来源期刊
CiteScore
5.70
自引率
9.70%
发文量
286
审稿时长
1 months
期刊介绍: The Journal of Assisted Reproduction and Genetics publishes cellular, molecular, genetic, and epigenetic discoveries advancing our understanding of the biology and underlying mechanisms from gametogenesis to offspring health. Special emphasis is placed on the practice and evolution of assisted reproduction technologies (ARTs) with reference to the diagnosis and management of diseases affecting fertility. Our goal is to educate our readership in the translation of basic and clinical discoveries made from human or relevant animal models to the safe and efficacious practice of human ARTs. The scientific rigor and ethical standards embraced by the JARG editorial team ensures a broad international base of expertise guiding the marriage of contemporary clinical research paradigms with basic science discovery. JARG publishes original papers, minireviews, case reports, and opinion pieces often combined into special topic issues that will educate clinicians and scientists with interests in the mechanisms of human development that bear on the treatment of infertility and emerging innovations in human ARTs. The guiding principles of male and female reproductive health impacting pre- and post-conceptional viability and developmental potential are emphasized within the purview of human reproductive health in current and future generations of our species. The journal is published in cooperation with the American Society for Reproductive Medicine, an organization of more than 8,000 physicians, researchers, nurses, technicians and other professionals dedicated to advancing knowledge and expertise in reproductive biology.
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