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. 2020 Sep;245(15):1355-1367.
doi: 10.1177/1535370220931035. Epub 2020 Jun 11.

GJB4 and GJC3 variants in non-syndromic hearing impairment in Ghana

Samuel M Adadey  1   2 , Kevin K Esoh, Osbourne Quaye  1 , Geoffrey K Amedofu, Gordon A Awandare  1 , Ambroise Wonkam  2
Affiliations

GJB4 and GJC3 variants in non-syndromic hearing impairment in Ghana

Samuel M Adadey et al. Exp Biol Med (Maywood). 2020 Sep.

Abstract

Although connexins are known to be the major genetic factors associated with HI, only a few studies have investigated GJB4 and GJC3 variants among hearing-impaired patients. This study is the first to report GJB4 and GJC3 variants from an African HI cohort. We have demonstrated that GJB4 and GJC3 genes may not contribute significantly to HI in Ghana, hence these genes should not be considered for routine clinical screening in Ghana. However, it is important to study a larger population to determine the association of GJB4 and GJC3 variants with HI.

Keywords: GJB4; GJC3; hearing impairment; in silico; protein modeling; virtual screening.

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Figures

Figure 1.
Figure 1.
Flow chart of genetic screening of patients with GJC3 and GJB4 variants, and in silico analysis of GJB4 c.356A>C (p.Asn119Thr) variant.
Figure 2.
Figure 2.
Chromatograms and multiple sequence alignment of GJB4 p.Asn119Thr variant. Chromatogram of Sanger sequence of (a) wild type and (b) mutant of GJB4 c.356A>C (p.Asn119Thr) variant. The position of the nucleotide change is highlighted in blue (c) Multiple sequence alignment of GJB4 protein in different species. Position 119 for the c.356A>C (p.Asn119Thr) variant is boxed.
Figure 3.
Figure 3.
Evaluation and validation of GJB4 protein models: ProsA web evaluation of (a) wildtype (p.Asn119=) and (b) mutant (p.Asn119Thr) proteins. Ramachandran plot of (c) wildtype (p.Asn119=) and (d) mutant (p.Asn119Thr) proteins. (e) Discrete optimized protein energy (DOPE) profile for wildtype (p.Asn119=) and mutant (p.Asn119Thr) proteins.
Figure 4.
Figure 4.
Refinement of GJB4 protein models. Galaxy refinement of (a) wild type and (b) mutant c.356A>C (p.Asn119Thr) GJB4 protein models. The best-ranked models are highlighted with red rectangles. Refined and unrefined models of (c) wild type and (d) mutant GJB4 c.356A>C (p.Asn119Thr) GJB4 protein models.
Figure 5.
Figure 5.
GJB4 mutant protein in complex with NEC. A LigPlus plot shows the interacting residues in detail.
See this image and copyright information in PMC

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Supplementary concepts