A novel dominant GJB2 (DFNA3) mutation in a Chinese family

Abstract

To decipher the phenotype and genotype of a Chinese family with autosomal dominant non-syndromic hearing loss (ADNSHL) and a novel dominant missense mutation in the GJB2 gene (DFNA3), mutation screening of GJB2 was performed on the propositus from a five-generation ADNSHL family through polymerase chain reaction amplification and Sanger sequencing. The candidate variation and the co-segregation of the phenotype were verified in all ascertained family members. Targeted genes capture and next-generation sequencing (NGS) were performed to explore additional genetic variations. We identified the novel GJB2 mutation c.524C > A (p.P175H), which segregated with high frequency and was involved in progressive sensorineural hearing loss. One subject with an additional c.235delC mutation showed a more severe phenotype than did the other members with single GJB2 dominant variations. Four patients diagnosed with noise-induced hearing loss did not carry this mutation. No other pathogenic variations or modifier genes were identified by NGS. In conclusion, a novel missense mutation in GJB2 (DFNA3), affecting the second extracellular domain of the protein, was identified in a family with ADNSHL.

<i>GJB2</i> Gene Related Nonsyndromic Hearing Loss in Mazandaran Province, North of Iran

“…In this study, 7 individuals from 3 families (7 out of 173 affected alleles) (4%) were seen with this mutation, with non-syndromic hearing loss ( Table 1 and Figure 1). To date, 54 dominant mutations in GJB2 gene have been identified worldwide (http://hereditaryhearingloss.org), of which about two-third can cause syndromic hearing loss and remaining causes autosomal dominant non-syndromic hearing loss [26] [45].…”

Clinical utility of Whole Exome Sequencing for rare Mendelian disorders: phenotypic-driven strategy for a high diagnostic yield and identification of 48 novel variants

“…Unlike recessive GJB2 variants, in which the spectrum and phenotype-genotype correlations have been analyzed clearly, only a few studies of GJB2 dominant variants have been reported. However approximately two-thirds of dominant GJB2 mutations are shown to cause syndromic hearing loss associated with diverse skin lesions(H. Wang et al, 2017).…”

On the Role of Fibrocytes and the Extracellular Matrix in the Physiology and Pathophysiology of the Spiral Ligament

“…GJB2 or GJB6, encoding for connexin 26 and 30, respectively, are two major deafness genes that induce a high incidence of non-syndromic hearing loss, both autosomal dominant (DFNA3) as recessive (DFNB1). However, there is also an association in syndromic hearing loss (80,81). Mutations in GJB2 and GJB6 cause a wide variety of phenotypes resulting in pre-or postlingual hearing loss ranging from mild to profound deafness (82).…”