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Background <p>Mutations in the <i>GJB2</i> (<i>connexin 26</i>) and <i>GJB6</i> (<i>connexin 30</i>) genes are the most common causes of congenital non-syndromic sensorineural hearing loss. More than 100 variants of the <i>GJB2</i> gene and two gene deletions of <i>GJB6</i> del(<i>GJB6-D13S1830</i>) and del(<i>GJB6-D13S1854</i>) have been reported in several countries.</p> <p>This study aims to look at the description and prevalence of <i>GJB2</i> and <i>GJB6</i> in patients with congenital non-syndromic sensorineural hearing loss (CNSHL) in Maluku, one of the Indonesian archipelago.</p> Patients and methods <p>This study was conducted on two groups, namely 40 patients with congenital non-syndromic sensory deafness (sporadic) and 40 populations of normal hearing. ENT examination, audiological evaluation, and identification of GJB2 mutations were performed by direct sequencing. <i>GJB6</i> examination using multiplex PCR to detect del(<i>GJB6-D13S1830</i>) and del(<i>GJB6-D13S1854</i>).</p> Results <p>From the results of the audiological examination, profound sensorineural hearing loss was observed in 37 of 40 patients (92.5%), while severe hearing loss was found in three patients (7.5%). Among 40 patients with congenital non-syndromic hearing loss (CNSHL), 30% had a <i>GJB2</i> mutation. Eight different genotypes were found in <i>GJB2</i>, including six novel genotypes: c.45delA, Pro187Leu, 78_79insC, 83_84insT, 166_167insC, and 290_291insA. The allelic frequency of c.45delA was 15%. The most common variant in Southeast Asia, Val37Ile, was present in 10% of CNSHL patients (4 of 40), with a carrier frequency of 2.5% in normal individuals. Additionally, mutations related to del(<i>GJB6-D13S18548</i>) were found in 10% of patients (4 out of 40), and del(<i>GJB6-D13S1830</i>) in 7.5% (3 out of 40), with carrier frequencies of 5% (2 out of 40) in normal individuals. Association mutations of <i>GJB2</i> with the GJB6 gene were observed in 7.5% of cases (3 out of 40), specifically involving the combinations Pro187Leu; del(<i>GJB6-D13S1830</i>), c.45delA; del(<i>GJB6-D13S1854</i>), and Val27Ile; del(<i>GJB6-D13S1830</i>). As many as 15% (6/40) of the composite mutations in both <i>GJB2</i> and <i>GJB6</i> genes, namely, (c.45delA; 78_79insC; 83_84insT), (c.45delA; 166_167insC), (c.45delA; 290_291insA), (c.45delA; Val37Ile), (c.45delA; 78_79insC), (del(<i>GJB6- D13S1854</i>); (<i>GJB6-D13S1830</i>)), all resulted in profound hearing loss.</p> Conclusion <p>The discovery of a mutation in <i>GJB2</i> accompanied by a <i>GJB6</i> mutation has the potential to cause non-syndromic congenital sensorineural deafness in Maluku. These results will contribute to increasing the knowledge and genetic populations of <i>GJB2</i> and <i>GJB6</i> worldwide.</p>

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The variants and prevalence of the GJB2 and GJB6 in patients with non-syndromic congenital sensorineural hearing loss in Maluku, Indonesia

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  • 发表日期：

    2025年10月6日

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  • Rodrigo Limmon,
  • Abdul Qadar Punagi,
  • Masyita Gaffar,
  • Irfan Idris,
  • Handayani Halik

摘要

Background

Mutations in the GJB2 (connexin 26) and GJB6 (connexin 30) genes are the most common causes of congenital non-syndromic sensorineural hearing loss. More than 100 variants of the GJB2 gene and two gene deletions of GJB6 del(GJB6-D13S1830) and del(GJB6-D13S1854) have been reported in several countries.

This study aims to look at the description and prevalence of GJB2 and GJB6 in patients with congenital non-syndromic sensorineural hearing loss (CNSHL) in Maluku, one of the Indonesian archipelago.

Patients and methods

This study was conducted on two groups, namely 40 patients with congenital non-syndromic sensory deafness (sporadic) and 40 populations of normal hearing. ENT examination, audiological evaluation, and identification of GJB2 mutations were performed by direct sequencing. GJB6 examination using multiplex PCR to detect del(GJB6-D13S1830) and del(GJB6-D13S1854).

Results

From the results of the audiological examination, profound sensorineural hearing loss was observed in 37 of 40 patients (92.5%), while severe hearing loss was found in three patients (7.5%). Among 40 patients with congenital non-syndromic hearing loss (CNSHL), 30% had a GJB2 mutation. Eight different genotypes were found in GJB2, including six novel genotypes: c.45delA, Pro187Leu, 78_79insC, 83_84insT, 166_167insC, and 290_291insA. The allelic frequency of c.45delA was 15%. The most common variant in Southeast Asia, Val37Ile, was present in 10% of CNSHL patients (4 of 40), with a carrier frequency of 2.5% in normal individuals. Additionally, mutations related to del(GJB6-D13S18548) were found in 10% of patients (4 out of 40), and del(GJB6-D13S1830) in 7.5% (3 out of 40), with carrier frequencies of 5% (2 out of 40) in normal individuals. Association mutations of GJB2 with the GJB6 gene were observed in 7.5% of cases (3 out of 40), specifically involving the combinations Pro187Leu; del(GJB6-D13S1830), c.45delA; del(GJB6-D13S1854), and Val27Ile; del(GJB6-D13S1830). As many as 15% (6/40) of the composite mutations in both GJB2 and GJB6 genes, namely, (c.45delA; 78_79insC; 83_84insT), (c.45delA; 166_167insC), (c.45delA; 290_291insA), (c.45delA; Val37Ile), (c.45delA; 78_79insC), (del(GJB6- D13S1854); (GJB6-D13S1830)), all resulted in profound hearing loss.

Conclusion

The discovery of a mutation in GJB2 accompanied by a GJB6 mutation has the potential to cause non-syndromic congenital sensorineural deafness in Maluku. These results will contribute to increasing the knowledge and genetic populations of GJB2 and GJB6 worldwide.