In Search of Genetic Markers for Nonsyndromic Deafness in Africa: A Study in Cameroonians and Black South Africans with the GJB6 and GJA1 Candidate Genes

Abstract

Deafness is the most common sensory disability in the world and has a variety of causes. Globally, mutations in GJB2 have been shown to play a major role in nonsyndromic deafness, but this has not been seen in Africans. Two other connexin genes, GJB6 and GJA1, have been implicated in hearing loss but have seldom been investigated in African populations. We set out to investigate the role of genetic variation in GJB6 and GJA1 in a group of Cameroonian and South African Blacks with nonsyndromic recessive hearing loss. A subset of 100 patients, affected with nonsyndromic hearing loss, from a cohort that was previously shown not to have GJB2 mutation, was analyzed by Sanger sequencing of the entire coding regions of GJB6 and GJA1. In addition, the large-scale GJB6-D3S1830 deletion was also investigated. No pathogenic mutation was detected in either GJB6 or GJA1, nor was the GJB6-D3S1830 deletion detected. There were no statistically significant differences in sequence variants between patients and controls. Mutations in GJB6 and GJA1 are not a major cause of nonsyndromic deafness in this group of Africans from Cameroon and South Africa. Currently, there is no sufficient evidence to support their testing in a clinical setting for individuals of African ancestry.

No evidence for clinical utility in investigating the connexin genes GJB2, GJB6 and GJA1 in non-syndromic hearing loss in black Africans

“…Similarly, no pathogenic variants were detected in GJA1, suggesting their nonimplication in hearing loss among the Cameroonians and black South Africans studied, [15] as has been reported in African Americans. [13] …”

“…[14] A subset of 100 selected patients, with deafness likely to be of genetic cause (mostly familial cases) and who did not have any mutation in GJB2 gene, were investigated for mutations in the GJB6 and GJA1 genes. [15] All the coding regions of GJB2, GJB6 and GJA1 were amplified and detection of del(GJB6-D13S1830) was also investigated. [14,15] In the GJB2 gene, two likely pathogenic mutations were detected in two unrelated Cameroonian participants, g.3741_3743delTTC (p.F142del) and g.3816G>A (p.V167M) in a single individual each and in the heterozygous state (Table 1).…”

“…[15] All the coding regions of GJB2, GJB6 and GJA1 were amplified and detection of del(GJB6-D13S1830) was also investigated. [14,15] In the GJB2 gene, two likely pathogenic mutations were detected in two unrelated Cameroonian participants, g.3741_3743delTTC (p.F142del) and g.3816G>A (p.V167M) in a single individual each and in the heterozygous state (Table 1). No pathogenic mutation was detected among the SA patients.…”

“…Only one variant (rs145762940) was detected, in the heterozygous state, in the coding region of GJB6, leading to the c.480G>A (p.G160=) change. [15] Equally, in the GJA1, five variants were detected; one of these occurred in the intron, but none were known to be pathogenic. [15] Few mutations in GJB2, GJB6 or GJA1 genes among other populations of African ancestry Our report and review of the literature confirmed that GJB2 gene is of little significance in non-syndromic hearing loss in populations of African descent (Table 1).…”

“…[15] Equally, in the GJA1, five variants were detected; one of these occurred in the intron, but none were known to be pathogenic. [15] Few mutations in GJB2, GJB6 or GJA1 genes among other populations of African ancestry Our report and review of the literature confirmed that GJB2 gene is of little significance in non-syndromic hearing loss in populations of African descent (Table 1). [10,14,[16][17][18][19][20] In addition, by combining data from previously unstudied deaf Xhosa patients in SA, Cameroonian patients, previous studies in Africans and the 1000 Genomes Project, …”