关键词: 听力障碍, 基因检测, 突变, 遗传咨询, 耳聋易感基因

Abstract:

Objective: To explore the applicability of the extended screening model to carry out screening of deafness susceptibility genes in pregnancy in Tianjin. Methods: Combined with the distribution of deafness gene mutation sites in Tianjin resident population obtained under the model of newborn hearing and gene screening, the susceptibility genes of 1 427 pregnant women and some of the spouses of pregnant women were tested for extended genetic deafness susceptibility genes. A total of 208 mutation sites in 24 genes related to deafness, including GJB2 and GJB3, were screened and analyzed by high-throughput sequencing. Positive results identified by high-throughput sequencing were further confirmed by Sanger sequencing. After verifying that the pregnant women were carriers of the disease-causing mutations on genes from the nuclear genome, their spouses were also analyzed via the same test scheme as described above, in addition to full-length analysis of the same gene identified in the female. Results: Among 1 427 pregnant women tested, 100 individuals with at least one pathogenic mutations of deafness genes were found by extended deafness gene screening, including 45 individuals with GJB2 gene mutations, 41 carriers of heterozygous mutations in the SLC26A4 gene, 2 carriers of heterozygous mutations in the TMPRSS3 gene, 1 carrier of LRTOMT gene mutation, and 11 individuals with homogeneous mutations on the mitochondrial gene MT-RNR1. Spouses of the above individuals with genomic deafness gene mutations were screened following the same procedures, and 6 deafness gene mutation carriers were detected, with 5 of them carrying mutations on the same gene as their spouses. Nine out of the 100 individuals detected by the extended screening scheme would have been missed using the original screening scheme, which only tests for 20 hotspot mutations from 4 target genes. Conclusions: Genetic screening for deafness related mutations in pregnant or pre-pregnant couples allows for earlier detection of potential birth defects, which can serve as a supplement to the newborn hearing concurrent gene screening program for hearing impairment. With advances in sequencing technology and decrease of sequencing costs, the application of extended screening scheme can help to identify additional carriers of deafness gene mutations missed by the original testing scheme.

Key words: Hearing disorders, Genetic testing, Mutation, Genetic counseling, Deafness susceptibility genes