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

Corresponding author: 王春玮, wangwei498000@126.com

DOI: 10.12201/bmr.202603.00067

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  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

  Submit time: 18 March 2026

  Copyright: The copyright holder for this preprint is the author/funder, who has granted biomedRxiv a license to display the preprint in perpetuity.
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