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目的拟采用新生儿脐带血,对常见耳聋突变位点进行筛查,探讨新生儿脐带血筛查的价值,并借此了解本地区常见耳聋基因的热点突变。方法收集冀南地区646例新生儿进行常规听力筛查,同时采集脐带血用于耳聋基因筛查。运用Mass ARRAY的i PLEX技术平台筛查4个常见耳聋基因(GJB2、GJB3、SLC26A4、mt DNA12SrRNA)中的20个最常见的热点突变位点。另外,用Sanger测序法检测mt DNA12SrRNA m.1494C>T和m.1555A>G两个位点。结果在646例新生儿中,11例(1.7%)未通过听力筛查。耳聋基因筛查发现这11例中有2例携带p.R143W纯合突变,1例携带GJB2基因c.235del C单杂合突变,1例携带GJB3基因p.R180X杂合致病突变。对于另外7例未发现已知热点突变的新生儿,通过对上述4个常见耳聋基因进行全测序,结果发现1例携带GJB2基因c.299-300del AT单杂合突变,1例携带p.V37I纯合致病突变,而其余5例新生儿在这4个基因中未检测到突变。在通过听力筛查的635例新生儿人群中,共有25例(3.9%)携带耳聋致病突变,突变率最高的是GJB2基因c.235del C杂合突变(12例,1.9%);其次是SLC26A4基因单杂合突变IVS7-2A>G(8例,1.3%),p.R409H 1例(0.2%),mt DNA12SrRNA位点m.1494C>T 2例(0.3%),m.1555A>G 2例(0.3%)。这些新生儿可能是潜在的耳聋患者。结论通过新生儿脐带血的基因筛查能够更早地发现对氨基糖甙类抗生素敏感性耳聋突变基因携带者,弥补听力筛查的不足,避免这些新生儿因使用氨基糖甙类抗生素致聋,可以有效防止或推迟耳聋的发生。
Objective To adopt neonatal umbilical cord blood to screen the common deafness mutation sites and investigate the value of cord blood screening in newborns and learn about the hot spot mutation of common deafness gene in this area. Methods A total of 646 newborns in the southern part of Hebei Province were collected for routine hearing screening and cord blood was collected for deafness gene screening. The 20 most common hot-spot mutations in four common deafness genes (GJB2, GJB3, SLC26A4, mt DNA12SrRNA) were screened using Mass ARRAY’s i PLEX technology platform. In addition, mt DNA12SrRNA m.1494C> T and m.1555A> G were detected by Sanger sequencing. Results Among 646 newborns, 11 (1.7%) failed hearing screening. Deafness gene screening found that 2 out of 11 cases carried p.R143W homozygous mutation, 1 case carried GJB2 gene c.235del C heterozygous mutation and 1 case carried GJB3 gene p.R180X heterozygous disease-causing mutation. For the other 7 cases of newborns who did not find the known hotspot mutations, by sequencing the 4 common deafness genes, one case of single heterozygous mutation of c.299-300del AT carrying GJB2 gene and one case of carrying p.V37I Homozygous disease-causing mutations, and the remaining five cases of newborns in these four genes did not detect mutations. Among 635 neonates who passed screening, 25 cases (3.9%) had deafness-causing mutations. The highest mutation rate was found in c.235delC heterozygous mutation of GJB2 gene (12 cases, 1.9%), followed by SLC26A4 gene single heterozygous mutation IVS7-2A> G (8 cases, 1.3%), p.R409H 1 case (0.2%), mt DNA12SrRNA site m.1494C> T 2 cases (0.3%), m.1555A> G 2 cases (0.3%). These newborns may be potentially deaf. Conclusion Neonatal umbilical cord blood gene screening can be more early detection of aminoglycoside susceptibility mutations in deafness gene carriers to make up for lack of hearing screening to prevent these neonates due to the use of aminoglycoside antibiotics deafness, Can effectively prevent or delay the occurrence of deafness.