Yuan Yongyi, Huang Deliang, Dai Pu, Zhu Xiuhui, Yu Fei, Zhang Xin, Liu Lixian, Han Dongyi
Department of Otolaryngology-Head and Neck Surgery, Otorhinolaryngology Institute, Genetic Testing Center for Deafness, PLA General Hospital, Beijing, 100853, China.
Lin Chuang Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2008 Jan;22(1):14-7, 21.
To investigate the genetic causes of nonsyndromic deaf patients in special educational school of Chifeng city. Inner Mongolia by genetic screening testing method. This study focused on analyzing mutations of coding sequence of GJB2, GJB3 and GJB6 gene.
DNA were extracted out from peripheral blood of 134 nonsyndromic deaf probands of Chifeng special educational school and 100 normal hearing controls in northern China. First, GJB2 gene mutation was analyzed by direct sequencing for its only exon in the open reading frame. Individuals found with heterozygous GJB2 mutation were given further testing for GJB6 del(GJB6-D13S1830) and direct sequencing for its exon. In 91 probands with unknown genetic cause (excluding probands who carried mtDNA A1555G mutation and GJB2 gene bi allele mutation and probands who were diagnosed as enlarged vestibular aqueduct by temporal CT), GJB3 gene mutation was analyzed by direct sequencing for its exon.
The sequencing results revealed that forty-one cases carried GJB2 mutation. of which twenty-two were homozygous or compound heterozygous and nineteen were heterozygous. Further testing for GJB6 del(GJB6-D13S1830) and analysis of its coding sequence in GJB2 heterozygous cases showed no positive result. Four subjects in control group carried pathogenetic mutation of GJB2 gene. Six types of novel variants of GJB2 gene were detected. Of the 91 deaf probands with unknown etiology. two probands were found carrying heterozygous pathogenetic mutation of GJB3 gene. one of whom also carried GJB2 235delC heterozygous mutation. One subjects in the control group carried pathogenetic mutation of GJB3 gene. Three types of novel variants of GJB3 gene were found.
By screening GJB2.GJB3 and GJB6 gene, we found 32.1% probands carrying GJB2, GJB3, and GJB6 mutations and we are able to determine genetic cause related to these three genes from one family for 16.42 percent of nonsyndromic deaf probands in special educational school of Chifeng city. The discovery of novel variants of GJB2 and GJB3 gene makes the mutational and polymorphic spectrum more plentiful in Chinese population.
采用基因筛查检测方法，研究内蒙古赤峰市特殊教育学校非综合征性耳聋患者的遗传病因。本研究重点分析GJB2、GJB3和GJB6基因编码序列的突变情况。
从赤峰特殊教育学校134例非综合征性耳聋先证者及中国北方100例正常听力对照者的外周血中提取DNA。首先，通过直接测序分析GJB2基因开放阅读框中的唯一外显子，检测其突变情况。对检测出GJB2基因杂合突变的个体，进一步检测GJB6 del(GJB6-D13S1830)，并对其外显子进行直接测序。在91例病因不明的先证者中（排除携带线粒体DNA A1555G突变、GJB2基因双等位基因突变以及经颞骨CT诊断为大前庭导水管综合征的先证者），通过直接测序分析GJB3基因外显子的突变情况。
测序结果显示，41例携带GJB2基因突变，其中22例为纯合或复合杂合突变，19例为杂合突变。对GJB2基因杂合突变个体进一步检测GJB6 del(GJB6-D13S1830)并分析其编码序列，未发现阳性结果。对照组中有4例携带GJB2基因致病突变。检测到GJB2基因6种新型变异。在91例病因不明的耳聋先证者中，2例携带GJB3基因杂合致病突变，其中1例还携带GJB2 235delC杂合突变。对照组中有1例携带GJB3基因致病突变。发现GJB3基因3种新型变异。
通过对GJB2、GJB3和GJB6基因进行筛查，我们发现32.1%的先证者携带GJB2、GJB3和GJB6基因突变，并且能够为赤峰市特殊教育学校16.42%的非综合征性耳聋先证者确定与这三个基因相关的遗传病因。GJB2和GJB3基因新型变异的发现使中国人群的突变和多态性谱更加丰富。
