GJB2 Is a Major Cause of Non-Syndromic Hearing Impairment in Senegal

Abstract

This study aimed to investigate GJB2 (MIM: 121011) and GJB6 (MIM: 604418) variants associated with familial non-syndromic hearing impairment (HI) in Senegal. We investigated a total of 129 affected and 143 unaffected individuals from 44 multiplex families by segregating autosomal recessive non-syndromic HI, 9 sporadic HI cases of putative genetic origin, and 148 control individuals without personal or family history of HI. The DNA samples were screened for GJB2 coding-region variants and GJB6-D3S1830 deletions. The mean age at the medical diagnosis of the affected individuals was 2.93 ± 2.53 years [range: 1–15 years]. Consanguinity was present in 40 out of 53 families (75.47%). Variants in GJB2 explained HI in 34.1% (n = 15/44) of multiplex families. A bi-allelic pathogenic variant, GJB2: c.94C>T: p.(Arg32Cys) accounted for 25% (n = 11/44 families) of familial cases, of which 80% (n = 12/15) were consanguineous. Interestingly, the previously reported “Ghanaian” founder variant, GJB2: c.427C>T: p.(Arg143Trp), accounted for 4.5% (n = 2/44 families) of the families investigated. Among the normal controls, the allele frequency of GJB2: c.94C>T and GJB2: c.427C>T was estimated at 1% (2/148 ∗ 2) and 2% (4/148 ∗ 2), respectively. No GJB6-D3S1830 deletion was identified in any of the HI patients. This is the first report of a genetic investigation of HI in Senegal, and suggests that GJB2: c.94C>T: p.(Arg32Cys) and GJB2: c.427C>T: p.(Arg143Trp) should be tested in clinical practice for congenital HI in Senegal.

Childhood Hearing Impairment in Senegal

“…Contrasting with reports from other SSA countries, where environmental factors remain a major cause of CHI, our study revealed a higher proportion of likely genetic etiology (52.7%), which is similar to reports from high-income settings [ 27 , 28 ]. This discrepancy might be due to the high consanguinity rate associated with a significant contribution of GJB2 to NSHI in the Senegalese population [ 22 ]. Moreover, Senegal is in an epidemiological transition phase characterized by the reduction of infectious diseases [ 29 ].…”

“…Moreover, there is not yet a universal newborn hearing screening program in Senegal. We recently showed that variants in GJB2 explained HI in 34.1% of the cases ( n = 15/44) in a select group of multiplex families in Senegal [ 22 ]. In order to get the full spectrum of CHI-associated etiologies across the country, we extended our recruitment to determine the clinical characteristics of CHI in Senegalese individuals living with HI.…”

Leveraging human–mouse studies to advance the genetics of hearing impairment in Africa

“…7 However, recently, mutations in the GJB2 gene were confirmed in NSHI in Senegal. 8 The genetic diversity of Africans and the complexity of the etiologies of HI cases could be contributing to the variability in detecting common NSHI causal mutations. 9,10 Nonetheless, the detection of novel genes for HI will benefit future initiatives regarding prevention, treatments, cure, care, or genetic counselling targeted towards Africans.…”

“…These variants account for most cases of NSHI in European and Asian populations but are rarely identified in SSA 7 . However, recently, mutations in the GJB2 gene were confirmed in NSHI in Senegal 8 . The genetic diversity of Africans and the complexity of the etiologies of HI cases could be contributing to the variability in detecting common NSHI causal mutations 9,10 .…”