Journal Article

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

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 KeCiang WANG YaoShen WANG ZhiLi PENG HongMei LUYanPing 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

2015

Overview

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.

• Publisher: Science China Press,Springer Nature B.V
• Subject: Aneuploidy / B2相 / Biomedical and Life Sciences / Biopsy / Cell-Free System / Connexin 26 / Connexins - genetics / Cover Article / DNA Mutational Analysis / Family Health / Female / Fertilization in Vitro / Hearing Loss - diagnosis / Hearing Loss - genetics / Hearing Tests / Humans / Life Sciences / Male / Mutation / Pedigree / PGD / Pregnancy / Pregnancy Outcome / Preimplantation Diagnosis - methods / Prenatal Diagnosis - methods / 三人家庭 / 产前诊断 / 听力障碍 / 整合 / 生殖 / 繁殖管理