Objective:To identify the pathogenic gene mutation of two patients with non-syndromic deafness（NSHL）. Methods:Two patient with NSHL and their parents were selected in the research object. Each participant provided 3-5 mL of peripheral venous blood, which was used to establish a DNA library. Next generation sequencing was used to detect the sequence of the patient's genome, and the sequencing results were compared with the human genome sequence （GRCh）37/hg19. Sanger sequencing was used to verify the parents' genome sequence. Finally the patient's pathogenic gene mutation was confirmed.Amino acid conservatism and single nucleotide polymorphisms of the mutant sites were analyzed using a variety of databases and software. Results:The mutation was located to CDH23 gene in the chromosomal location 10q21-q22. Complex heterozygous mutations consist of c. 1343T>C and c. 7991_7993delTCA. Parents are heterozygous carriers of a single mutation. Conclusion:The next generation sequencing technology were used to screen the pathogenic gene mutation of inherited deafness. Combined with the genetic sequencing results of parents, the specific pathogenic gene mutation of deafness patients can be identified. While the pathogenicity of complex heterozygous mutation were explained by various pathogenicity analysis methods.
目的：研究2例非综合征性耳聋（NSHL）患儿的致病突变基因。 方法：以2例临床诊断为NSHL的姐妹及其父母为研究对象，采集其3～5 mL外周静脉血，建立基因组DNA文库，使用高通量测序平台进行突变检测，测序结果和人类基因组序列（GRCh）37/hg19进行比对，锁定该患儿可能的致病基因及突变位点，并进一步采用Sanger测序技术对患儿父母进行相关突变位点的验证，最终确定该患儿的致病基因；通过单核苷酸多态性位点分析、氨基酸保守性分析、氨基酸序列分析及蛋白质结构三维建模等手段，分析复合杂合突变的致病机制。 结果：该患儿致病突变定位于10q21-q22的CDH23基因，由c.1343T>C和c.7991_7993delTCA两个位点组成的复合杂合突变致病；患儿父母为单个突变的杂合携带者。 结论：使用高通量测序技术可以对遗传性聋患儿致病基因突变进行筛查，结合父母基因测序结果，可明确耳聋患儿具体致病基因突变；通过多种致病分析方式，可以尝试解释复合杂合突变的致病原因。.
Keywords: non-syndromic hearing loss; CDH23; gene mutation; hereditary deafness.
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