The prevalence of common genetic deafness related mutation detected by microarray and follow-up in pregnant women in Beijing

Abstract

Objective To determine the distribution of common deafness gene mutations by microarray-PCR in pregnant women of Beijing, then explore their prevalence and clinical significance. Methods Totally 1 709 pregnant women were prospectively enrolled from the outpatients of Obstetrical Clinical from Peking University Peoples′ Hospital in this study from June 2016 to April 2018. Peripheral blood samples were obtained and DNA templates were extracted from all subjects. The coding region of the GJB2 gene(35del G, 235delC, 176-191del16, 299-300delAT), SLC26A4 gene (IVS7-2 A>G,2168A>G) , 12sRNA gene (1494C>T,1555A>G) and GJB3 gene (538 C>T) were detected by microarray-PCR. Meanwhile, 256 cases firstly recruited in this study were confirmed by Sanger sequencing. The analysis was performed to explore the distribution of deafness gene mutations and the subjects detected to be positive were further followed up until they had given birth to their babies. Results Among 1 709 pregnant women, 89 cases were found to be carrying at least one mutation sites(5.21%).Among them,83 cases were heterozygous mutation(35 cases of GJB2 235delC, 12 cases of GJB2 299-300delAT mutation, one case of GJB2 176-191del 16, 30 cases of SLC26A4 IVS 7-2 A>G, 3 cases of SLC26A4 2168 A>G and two cases of GJB3 538 C>T). There were one case of 235delC homozygous mutation and 2 cases of double mutations(IVS7 -2 A>G/GJB2 299-300delAT, IVS7 -2 A>G/GJB2 235delC). The positive rate of 235delC, 299-300delAT and 176-191del16 was 2.17%, 0.76% and 0.06%, respectively. As to SLC26A4, 1.87% of the pregnant women were carrying IVS 7-2 A>G and 0.18% for 2168 A>G. Two cases were detected carrying GJB3 C>T mutation and three for 12s RNA1555 A>G mutation, respectively. The results of microarray-PCR were identical to those of Sanger sequencing, with the coincidence of 100%.26 spouses of the 56 cases were followed up. Two proved to be carrier of the same gene mutation. One of their babies was born with normal hearing until the end of this research, while another baby was born deafness and implant cochlear when three month old. Conclusions GJB2 235delC and SLC26A4 IVS 7-2 A>G were the most prevalent mutations in pregnant women of Beijing, and it may provide guidance to eugenics and early clinical intervention. Key words: Microarray analysis; Deafness; Connexins; Sulfate transporters; Mutation; Sequence analysis, DNA; Follow-up studies