Reproductive management through integration of PGD and MPS-based noninvasive prenatal screening/diagnosis for a family with GJB2-associated hearing impairment  

作　　者：XIONG WenPing WANG DaYong GAO Yuan GAO Ya WANG HongYang GUAN Jing LAN Lan YAN JunHao ZONG Liang YUAN Yuan DONG Wei HUANG SeXin WU KeLiang WANG YaoShen WANG ZhiLi PENG HongMei LU YanPing XIE LinYi ZHAO Cui WANG Li ZHANG QiuJing GAO Yun LI Na YANG Ju YIN ZiFang HAN Bing WANG Wei CHEN Zi-Jiang WANG QiuJu 

机构地区：[1]Department of Otolaryngology-Head and Neck Surgery, Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital [2]Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University [3]National Research Center for Assisted Reproductive Technology and Reproductive Genetics [4]BGI-Shenzhen [5]Department of Ultrasonography, Chinese PLA General Hospital [6]Department of Obstetrics and Gynecology, Chinese PLA General Hospital [7]The Key laboratory for Reproductive Endocrinology of Ministry of Education

出　　处：《Science China(Life Sciences)》2015年第9期829-838,共10页中国科学（生命科学英文版）

基　　金：supported by the National Program on Key Basic Research Project(2014CB943001 and 2012CB944700);the National Natural Science Foundation of China(81120108009 and 81530032);the National Health and Family Planning Commission of the People's Republic of China(201402004);Science and Technology Plan of Guangdong Province(2013B022000005);Guangdong Enterprise Key Laboratory of Human Disease Genomics(2011A060906007);Shenzhen Engineering Laboratory for Birth Defects Screening([2011]861)

摘　　要：A couple with a proband child of GJB2 （encoding the gap junction protein connexin 26）-associated hearing impairment and a previous pregnancy miscarriage sought for a reproductive solution to bear a healthy child. Our study aimed to develop a cus- tomized preconception-to-neonate care trajectory to fulfill this clinical demand by integrating preimplantation genetic diagno- sis （PGD）, noninvasive prenatal testing （NIPT）, and noninvasive prenatal diagnosis （N1PD） into the strategy. Auditory and ge- netic diagnosis of the proband child was carried out to identify the disease causative mutations. The couple then received in-vitro-fertilization treatment, and eight embryos were obtained for day 5 biopsy. PGD was performed by short-tandem-repeat linkage analysis and Sanger sequencing of GJB2 gene. Transfer of a GJB2c.235delC heterozygous embryo resulted in a sin- gleton pregnancy. At the 13th week of gestation, genomic DNA （gDNA） from the trio family and cell-free DNA （cfDNA） from maternal plasma were obtained for assessment of fetal chromosomal aneuploidy and GJB2 mutations. NIPT and NIPD showed the absence of chromosomal aneuploidy and GJB2-associated disease in the fetus, which was later confirmed by inva- sire procedures and postnatal genetic/auditory diagnosis. This strategy successfully prevented the transmission of hearing im- pairment in the newborn, thus providing a valuable experience in reproductive management of similar cases and potentially other monogenic disorders.A couple with a proband child of GJB2(encoding the gap junction protein connexin 26)-associated hearing impairment and a previous pregnancy miscarriage sought for a reproductive solution to bear a healthy child. Our study aimed to develop a customized preconception-to-neonate care trajectory to fulfill this clinical demand by integrating preimplantation genetic diagnosis(PGD), noninvasive prenatal testing(NIPT), and noninvasive prenatal diagnosis(NIPD) into the strategy. Auditory and genetic diagnosis of the proband child was carried out to identify the disease causative mutations. The couple then received in-vitro-fertilization treatment, and eight embryos were obtained for day 5 biopsy. PGD was performed by short-tandem-repeat linkage analysis and Sanger sequencing of GJB2 gene. Transfer of a GJB2 c.235del C heterozygous embryo resulted in a singleton pregnancy. At the 13 th week of gestation, genomic DNA(g DNA) from the trio family and cell-free DNA(cf DNA) from maternal plasma were obtained for assessment of fetal chromosomal aneuploidy and GJB2 mutations. NIPT and NIPD showed the absence of chromosomal aneuploidy and GJB2-associated disease in the fetus, which was later confirmed by invasive procedures and postnatal genetic/auditory diagnosis. This strategy successfully prevented the transmission of hearing impairment in the newborn, thus providing a valuable experience in reproductive management of similar cases and potentially other monogenic disorders.

关 键 词：preimplantation genetic diagnosis(PGD) noninvasive prenatal testing(NIPT) noninvasive prenatal diagnosis(NIPD) GJB2(encoding the 

分 类 号：R714.5[医药卫生—妇产科学]