广西壮族自治区南宁市新生儿GJB2致聋基因的携带研究

Study on the Carrying of GJB2 Deafness Gene in Newborns of Nanning City

目的探讨南宁市新生儿GJB2致聋基因携带状况和突变位点与耳聋相关性。方法收集2016~2018年期间在南宁市新生儿疾病筛查中心进行听力筛查未通过的1007例新生儿血液,制成干血斑纸片,提取DNA,采用测序法进行GJB2全基因测序。统计新生儿GJB2基因突变的携带率,并结合新生儿听力损失确诊情况分析致聋基因突变特点。结果1007例新生儿中GJB2致聋基因突变携带率为55.21%(556/1007),检测出GJB2基因突变位点16个,其中GJB2 c.109 G>A突变携带率较高,占20.36%,其次是c.79 G>A占10.03%,c.608 T>C占7.65%,c.217 C>A占7.15%,c.341 A>G占6.85%,其它位点(包括c.11 G>A,c.-23+1 G>A,c.235del C,c.299 del AT,c.-121 G>A,c.464 A>G,c.147 C>G,c.676 G>T,c.316 T>G,c.-23-35 G>T和c.368 C>A)突变携带率<0.1%。556例GJB2致聋基因突变者中有31例确诊为不同程度耳聋,4个致聋突变位点包括GJB2 c.109 G>A(26例),c.11 G>A(2例),c.235del C(2例)和c.299 del AT(1例),分别占耳聋患者比率是83.87%,6.45%,6.45%和3.23%。81例检出6个新突变位点c.-23-35 G>T,c.-121 G>A,c.464 A>G,c.217 C>A,c.147 C>G和c.676 G>T及4例检出1个未明确致病性位点c.-23+1 G>A,另外有250例检出5个常见多态性突变位点。GJB2 c.109 G>A携带率与北京、台湾和上海比较差异有统计学意义(χ^2=133.364,11.724,32.449,均P<0.05)。结论南宁市新生儿GJB2致聋基因携带率较高,筛查出4个致聋突变位点,6个新突变位点及1个未明确致病位点,明确了致聋突变位点以c.109 G>A纯合子突变为主,基因突变特点有明显的地域性差异。

Objective To investigate the relationship between the carrying status and mutation site of GJB2 deafness gene in newborn infants in Nanning city. Methods The blood of 1 007 newborns who failed hearing screening in Nanning neonatal disease screening center from 2016 to 2018 was collected and maded into dried blood stains,then the DNA was extracted,and the GJB2 gene was sequenced by whole genome sequencing method. The carrying rate of newborn GJB2 genemutation was calculated,and the characteristics of deafness gene mutation were analyzed based on the confirmed hearing loss of newborn.Results The carrying rate of GJB2 deafness gene mutation in 1 007 newborns was 55. 21%( 556/1 007). Sixteen mutations of GJB2 gene were detected,among the mutation rate of GJB2 c. 109 G > A was higher,accounting for 20. 36%,followed by10. 03% of GJB2 c. 79 G > A,7. 65% of c. 608 T > C,7. 15% of c. 217 C > A,and 6. 85% of c. 341 A > G. Mutation carrying rate of other sites < 0. 1%( including c. 11 G > A,c.-23 + 1 G > A,c. 235 del C,c. 299 del AT,c.-121 G > A,c. 464 A > G,c. 147 C > G,c. 676 G > T,c. 316 T > G,c.-23-35 G > T and c. 368 C > A). Among the 556 patients with GJB2-induced deafness gene mutation,31 patients were diagnosed with different degrees of deafness,and 4 mutations including GJB2 c. 109 G > A( 26 cases),c. 11 G > A( 2 cases) c. 235 del C( 2 cases) and c. 299 del AT( 1 case) accounted for83. 87%,6. 45%,6. 45% and 3. 23% respectively. Six new mutations including GJB2 c.-23-35 G > T,c.-121 G > A,c.464 A > G,c. 217 C > A,c. 147 C > G and c. 676 G > T were detected in 81 cases and one undefined pathogenicity locus c.-23 + 1 G > A was detected in 4 cases,and five common polymorphism mutations were detected in 250 cases. The carrying rate of GJB2 c. 109 G > A was statistically significant compared with other cities in China. Conclusion The carrying rate of GJB2 deafness gene in neonates in Nanning city is higher. There are 4 deafness mutation sites,6 new mutation sites and 1 undefined pathogenic site have been screened out. It is clear that the deafness mutation sites are dominated by c. 109 G > A homozygous mutation,and the gene mutation characteristics have obvious regional differences.