title: Reproductive management through integration of PGD and MPS-based noninvasive prenatal screening/diagnosis for a family with GJB2-associated hearing impairment.
abstract: 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 GJB2c.235delC heterozygous embryo resulted in a singleton 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 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.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, 100853, China.
authors.forename: WenPing
authors.initials: W
authors.lastname: Xiong
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, 100853, China.
authors.forename: DaYong
authors.initials: D
authors.lastname: Wang
authors.affiliation: Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, China.|National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan, 250021, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: BGI-Shenzhen, Shenzhen, 518083, China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, 100853, China.
authors.forename: HongYang
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, 100853, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Guan
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, 100853, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Lan
authors.affiliation: Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, China.|National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan, 250021, China.
authors.forename: JunHao
authors.initials: J
authors.lastname: Yan
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, 100853, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zong
authors.affiliation: BGI-Shenzhen, Shenzhen, 518083, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: BGI-Shenzhen, Shenzhen, 518083, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Dong
authors.affiliation: Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, China.|National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan, 250021, China.
authors.forename: SeXin
authors.initials: S
authors.lastname: Huang
authors.affiliation: Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, China.|National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan, 250021, China.
authors.forename: KeLiang
authors.initials: K
authors.lastname: Wu
authors.affiliation: BGI-Shenzhen, Shenzhen, 518083, China.
authors.forename: YaoShen
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Ultrasonography, Chinese PLA General Hospital, Beijing, 100853, China.
authors.forename: ZhiLi
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, Chinese PLA General Hospital, Beijing, 100853, China.
authors.forename: HongMei
authors.initials: H
authors.lastname: Peng
authors.affiliation: Department of Obstetrics and Gynecology, Chinese PLA General Hospital, Beijing, 100853, China.
authors.forename: YanPing
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, 100853, China.
authors.forename: LinYi
authors.initials: L
authors.lastname: Xie
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, 100853, China.
authors.forename: Cui
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, 100853, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, 100853, China.
authors.forename: QiuJing
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, 100853, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, 100853, China.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, 100853, China.
authors.forename: Ju
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, 100853, China.
authors.forename: ZiFang
authors.initials: Z
authors.lastname: Yin
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, 100853, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Han
authors.affiliation: BGI-Shenzhen, Shenzhen, 518083, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, China. chenzijiang@hotmail.com.|National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan, 250021, China. chenzijiang@hotmail.com.|The Key laboratory for Reproductive Endocrinology of Ministry of Education, Jinan, 250021, China. chenzijiang@hotmail.com.
authors.forename: Zi-Jiang
authors.initials: ZJ
authors.lastname: Chen
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, 100853, China. wqcr301@sina.com.
authors.forename: QiuJu
authors.initials: Q
authors.lastname: Wang
mesh_terms: D000782:Aneuploidy; D001706:Biopsy; D002474:Cell-Free System; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D005307:Fertilization in Vitro; D034381:Hearing Loss / Q000175:diagnosis* / Q000235:genetics; D006320:Hearing Tests; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D011247:Pregnancy; D011256:Pregnancy Outcome; D019836:Preimplantation Diagnosis / Q000379:methods*; D011296:Prenatal Diagnosis / Q000379:methods
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26
keywords: GJB2 (encoding the gap junction protein connexin 26); hearing impairment; noninvasive prenatal diagnosis (NIPD); noninvasive prenatal testing (NIPT); preimplantation genetic diagnosis (PGD)