通讯作者: 王春玮, wangwei498000@126.com

DOI：10.12201/bmr.202603.00067

Genetic Analysis of a Deafness Family with Mitochondrial m.1555A>G and GJB2 c.235delC Mutations

• 摘要：目的 以1个含9名成员先天性聋哑夫妇核心家系为研究对象，系统解析线粒体基因m.1555A>G与GJB2基因c.235delC位点的分子特征、致病机制、遗传传递规律，及突变类型与听力表型的关联性，为临床遗传咨询与产前干预提供依据。方法 通过聚合酶链反应-反向斑点杂交法（PCR-RDB）检测GJB2、GJB3、SLC26A4、mtRNA等基因的20个耳聋热点突变位点，结合临床资料、近年文献报道案例及致病机制，进行遗传模式推导与表型-基因型关联分析。结果 先证者为c.235delC纯合突变（先天性聋哑），成员1（先证者丈夫）为m.1555A>G均质型突变（先天性聋哑），成员3（先证者丈夫的母亲）为m.1555A>G均质型突变（听力正常）；成员4（先证者父亲）、成员5（先证者母亲）为c.235 del C位点杂合突变（听力正常）；成员6（先证者大女儿）、成员7（先证者儿子）、成员8（先证者小女儿）均为c.235 del C杂合突变（成员6行人工耳蜗植入，新生儿子女暂无听力异常）；成员2（先证者丈夫的父亲）无上述位点突变（听力正常）。结论 该家系耳聋由双致病突变位点分别导致，m.1555A>G遵循母系遗传，c.235delC遵循常染色体隐性遗传；两种突变的致病机制存在本质差异，表型表达受突变类型、遗传背景及环境因素调控；PCR-RDB技术可作为耳聋基因的初筛手段，检测针对预设的耳聋基因热点突变，为家系病因诊断提供较可靠支撑，但其检测范围的局限性，在临床实践中需结合患者临床表型、家族遗传史及多种检测技术的结果，为遗传性耳聋患者提供精准的病因诊断、遗传咨询及干预指导。

  关键词： 遗传性耳聋；线粒体基因；GJB2基因；m.1555A>G突变；c.235delC突变；家系遗传分析；聚合酶链反应-反向点杂交; ; ; ; 

   

  Abstract: Objective Taking a congenital deaf-mutism family with 9 members as the research subject, this study systematically analyzed the molecular characteristics, pathogenic mechanisms, genetic transmission rules of the mitochondrial gene m.1555A>G and the GJB2 gene c.235delC locus, as well as the correlation between mutation types and hearing phenotypes, so as to provide a basis for clinical genetic counseling and prenatal intervention. Methods A total of 20 deafness hotspot mutation loci in GJB2, GJB3, SLC26A4 and mtRNA genes were detected by polymerase chain reaction-reverse dot blot (PCR-RDB). Combined with clinical data, reported cases in recent literatures and pathogenic mechanisms, genetic pattern deduction and phenotype-genotype correlation analysis were performed. Results The proband carried homozygous mutation of c.235delC (congenital deaf-mutism). Member 1 (the proband’s husband) had homoplasmic mutation of m.1555A>G (congenital deaf-mutism), while Member 2 (the husband’s mother of the proband) also carried homoplasmic mutation of m.1555A>G but with normal hearing. Member 4 (the proband’s father) and Member 5 (the proband’s mother) were heterozygous for the c.235delC locus and showed normal hearing. Member 6 (the proband’s eldest daughter), Member 7 (the proband’s son) and Member 8 (the proband’s youngest daughter) all carried heterozygous mutation of c.235delC; among them, Member 6 received cochlear implantation, and the newborn children had no hearing impairment so far. Member 3 (the husband’s father of the proband) had no mutations at the above-mentioned loci and presented with normal hearing. Conclusion Deafness in this family is caused by two separate pathogenic mutation loci. The m.1555A>G mutation follows maternal inheritance, while the c.235delC mutation conforms to autosomal recessive inheritance. The pathogenic mechanisms of the two mutations are essentially different, and phenotypic expression is regulated by mutation types, genetic background and environmental factors. PCR-RDB technology can be used as a primary screening method for deafness genes. It detects pre-set hot spot mutations of deafness genes and provides relatively reliable support for the etiological diagnosis of families. However, due to its limitation in detection scope, in clinical practice, it is necessary to combine the patients clinical phenotype, family medical history and the results of various detection technologies to provide accurate etiological diagnosis, genetic counseling and intervention guidance for patients with hereditary deafness.

  Key words: hereditary deafness; mitochondrial genes; GJB2；m.1555A>G；c.235delC; family genetic analysis; PCR-RDB

  提交时间：2026-03-18

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• 序号	提交日期	编号	操作
  1	2026-01-30	10.12201/bmr.202603.00067V1	下载

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