[Primary prevention study of preimplantation genetic testing for GJB2 gene mutation families]

Objective: This study aimed to investigate the families with different GJB2 gene mutations undergoing preimplantation genetic testing (PGT), in order to provide reference for clinical practice and implementation strategies. Methods: Five families undergoing PGT for GJB2 gene mutations at Chinese People's Liberation Army (PLA) General Hospital from 2015 to 2024 were selected. All families received genetic counseling, and the audiological data of the patients and their relatives were collected. Blood samples from the probands and their related family members were taken for genetic sequencing. After entering the PGT process, oocyte retrieval, in vitro fertilization, embryo biopsy, and genetic testing were performed. Healthy embryos were selected for transfer, and the pregnant women were followed up. Results: The 5 families included in the study were as follows: one family with both parents being carriers of GJB2 c.235delC, one family with both parents being carriers of GJB2 c.109G>A, one family with one parent affected by autosomal dominant inheritance of GJB2, and in two other families, the probands were married to each other, and both GJB2 and SLC26A4 gene mutations were involved. Through different PGT strategies, the five families underwent a total of four assisted reproductive cycles, all of which resulted in clinical pregnancies. Four couples had delivered four healthy offsprings, all of whom passed hearing screening. Conclusions: GJB2 gene mutations, due to their involvement in diverse phenotypes, varying disease severity, and different inheritance patterns, require careful consideration when performing PGT. Different linkage analysis strategies should be chosen for families with varying genetic inheritance modes. For GJB2 c.109G>A with milder phenotypes, it is not recommended to proactively suggest prenatal or preimplantation interventions during genetic counseling, unless the couple strongly requests it, in which case, thorough genetic counseling and informed consent, should be obtained. Additionally, PGT may be performed for GJB2 c.109G>A concurrently if the couple is involved in other high-risk genetic diseases.