GJB2 and GJB6 Mutations in Hereditary Recessive Non-Syndromic Hearing Impairment in Cameroon

Abstract

This study aimed to investigate GJB2 (connexin 26) and GJB6 (connexin 30) mutations associated with familial non-syndromic childhood hearing impairment (HI) in Cameroon. We selected only families segregating HI, with at least two affected individuals and with strong evidence of non-environmental causes. DNA was extracted from peripheral blood, and the entire coding region of GJB2 was interrogated using Sanger sequencing. Multiplex PCR and Sanger sequencing were used to analyze the prevalence of the GJB6-D3S1830 deletion. A total of 93 patients, belonging to 41 families, were included in the analysis. Hearing impairment was sensorineural in 51 out of 54 (94.4%) patients. Pedigree analysis suggested autosomal recessive inheritance in 85.4% (35/41) of families. Hearing impairment was inherited in an autosomal dominant and mitochondrial mode in 12.2% (5/41) and 2.4% (1/41) of families, respectively. Most HI participants were non-syndromic (92.5%; 86/93). Four patients from two families presented with type 2 Waardenburg syndrome, and three cases of type 2 Usher syndrome were identified in one family. No GJB2 mutations were found in any of the 29 families with non-syndromic HI. Additionally, the GJB6-D3S1830 deletion was not identified in any of the HI patients. This study confirms that mutations in the GJB2 gene and the del(GJB6-D13S1830) mutation do not contribute to familial HI in Cameroon.

Hearing Impairment Overview in Africa: the Case of Cameroon

“…Pure tone audiometry (PTA) was the most frequent tool used to diagnose HI. The study quality was high, moderate and low in ten [26][27][28][29][30][31][32][33][34][35], three [36][37][38] and four [39][40][41][42] studies, respectively.…”

“…In Cameroon, sensorineural HI is the most frequent pathophysiological type, and is accounted for in 61.7% to 94.4% of all HI cases, while mixed and conductive HI are found in 5.6% to 20% and 0% to 18.3% of cases, respectively [26,27,29]. HI tend to be more severe in school settings, where profound HI (≥81 dB) accounts for 93.5% to 98.2% of cases [27,29,36], than in community settings, where profound HI is observed in only 9% of cases, the majority (76%) being moderate HI (41-60 dB) [32]. Bilateral HI represent 36% to 100% of cases [26,27,29,36]; and in the case-control study performed in a referral hospital of Yaoundé, HI was left-sided and right-sided in 43% and 21% of participants, respectively [26].…”

“…Concerning hereditary HI, NSHI is the most prevalent clinical entity in Cameroon, and accounts for 86.1% to 92.5% of cases, while syndromic HI represents 7.5% to 13.9% of cases [27,29].…”

“…Waardenburg syndrome (WS) is the most frequent syndromic HI in the Cameroonian population; it represents 1% of all HI cases, 4.3% to 7% of HI of genetic origin, and 50% to 57.14% of genetic syndromic cases [27,29,35]. All cases of WS described in the Cameroonian population are type 2 (without dystopia canthorum).…”

“…All cases of WS described in the Cameroonian population are type 2 (without dystopia canthorum). Clinical signs included: congenital severe to profound sensorineural HI, hypopigmentation of the skin (usually on the trunk), premature canitis, isochromic sapphire-blue eyes and in some cases heterochromia iridis that can be segmental or complete (Figure 2) [27,29,35].…”