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

Wonkam, Ambroise; Bosch, Jason; Noubiap, Jean Jacques; Lebeko, Kamogelo; Makubalo, Nomlindo; Dandara, Collet

doi:10.7196/samj.8814

Cited by 24 publications

(20 citation statements)

References 23 publications

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“…Although mitochondrial mutations in MT-RNR1 may increase genetic susceptibility, 36,37 this is more prevalent in Europeans and Asians and not in sub-Saharan Black Africans, among whom the prevalence of this mutation is extremely low (0–0.09%). 37–40 …”

Section: Discussionmentioning

confidence: 99%

Increased risk of aminoglycoside-induced hearing loss in MDR-TB patients with HIV coinfection

Hong¹,

Budhathoki²,

Farley

2018

int j tuberc lung dis

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SUMMARY Setting A high proportion of individuals with multi-drug-resistant tuberculosis (MDR-TB) develop permanent hearing loss due to ototoxicity caused by injectable aminoglycosides (AGs). The prevalence of AG-induced hearing loss is greatest in tuberculosis (TB) and human immunodeficiency virus (HIV) endemic countries in sub-Saharan Africa. However, whether HIV coinfection is associated with a higher incidence of AG-induced hearing loss during MDR-TB treatment is controversial. Objective To evaluate the impact of HIV coinfection on AG-induced hearing loss among individuals with MDR-TB in sub-Saharan Africa. Design This was a meta-analysis of articles published in PubMed, Embase, Scopus, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Cochrane Review, and reference lists using search terms ‘hearing loss’, ‘aminoglycoside’, and ‘sub-Saharan Africa’. Results Eight studies conducted in South Africa, Botswana and Namibia and published between 2012 and 2016 were included. As the included studies were homogeneous (χ2=8.84, d.f.=7), a fixed-effects model was used. Individuals with MDR-TB and HIV coinfection had a 22% higher risk of developing AG-induced hearing loss than non-HIV-infected individuals (pooled relative risk=1.22; 95% CI=1.10–1.36) during MDR-TB treatment. Conclusion This finding is critical for TB programs with regard to the expansion of injectable-sparing regimens. Our findings lend credibility to using inject- able-sparing regimens and more frequent hearing monitoring, particularly in resource-limited settings for HIV-coinfected individuals.

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Section: Discussionmentioning

confidence: 99%

Increased risk of aminoglycoside-induced hearing loss in MDR-TB patients with HIV coinfection

Hong¹,

Budhathoki²,

Farley

2018

int j tuberc lung dis

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“…17 Nevertheless,mutations in GJB6 is not a major cause of non-syndromic deafness in black Africans. 18 Enlarged and hyperproliferative sebaceous glands have not been reported in patients with HED, whether this phenomenon can occur in human need further observation and investigation. Amy C. Berger argued that the A88V mutant remain in intracellular compartments, but could be trafficked to the cell surface.…”

Section: Discussionmentioning

confidence: 97%

“…A mouse model for Clouston syndrome carrying the GJB6 mutation A88V developed enlarged and hyperproliferative sebaceous glands and represented an altered hearing profile . Nevertheless,mutations in GJB6 is not a major cause of non‐syndromic deafness in black Africans …”

Section: Discussionmentioning

confidence: 99%

A known mutation in GJB6 in a large Chinese family with hidrotic ectodermal dysplasia

Yang

Kong

et al. 2016

Acad Dermatol Venereol

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“…Thus, the GJB6 gene itself plays no role in the development of hearing impairment but the surrounding sequences consisting of the cis-acting elements are responsible for the development of hearing impairment [5,6]. Nevertheless, in most African populations, GJB2 and GJB6 variants are rarely implicated in hearing impairment [7,8] with some GJB2 cases found in Morocco [9,10], Sudan, and Kenya [11], yet an exceptionally high prevalence is found in Ghana [12][13][14]. Indeed, in Ghana, GJB2 mutation (p.Arg143Trp) in the homozygous state accounts for 25.9% of cases in families segregating non-syndromic HI, as well as 7.9% of non-familial non-syndromic congenital HI cases (Adadey et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Enhancing Genetic Medicine: Rapid and Cost-Effective Molecular Diagnosis for a GJB2 Founder Mutation for Hearing Impairment in Ghana

Adadey

Wonkam

Aboagye

et al. 2020

Genes

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In Ghana, gap-junction protein β 2 (GJB2) variants account for about 25.9% of familial hearing impairment (HI) cases. The GJB2-p.Arg143Trp (NM_004004.6:c.427C>T/OMIM: 121011.0009/rs80338948) variant remains the most frequent variant associated with congenital HI in Ghana, but has not yet been investigated in clinical practice. We therefore sought to design a rapid and cost-effective test to detect this variant. We sampled 20 hearing-impaired and 10 normal hearing family members from 8 families segregating autosomal recessive non syndromic HI. In addition, a total of 111 unrelated isolated individuals with HI were selected, as well as 50 normal hearing control participants. A restriction fragment length polymorphism (RFLP) test was designed, using the restriction enzyme NciI optimized and validated with Sanger sequencing, for rapid genotyping of the common GJB2-p.Arg143Trp variant. All hearing-impaired participants from 7/8 families were homozygous positive for the GJB2-p.Arg143Trp mutation using the NciI-RFLP test, which was confirmed with Sanger sequencing. The investigation of 111 individuals with isolated non-syndromic HI that were previously Sanger sequenced found that the sensitivity of the GJB2-p.Arg143Trp NciI-RFLP testing was 100%. All the 50 control subjects with normal hearing were found to be negative for the variant. Although the test is extremely valuable, it is not 100% specific because it cannot differentiate between other mutations at the recognition site of the restriction enzyme. The GJB2-p.Arg143Trp NciI-RFLP-based diagnostic test had a high sensitivity for genotyping the most common GJB2 pathogenic and founder variant (p.Arg143Trp) within the Ghanaian populations. We recommend the adoption and implementation of this test for hearing impairment genetic clinical investigations to complement the newborn hearing screening program in Ghana. The present study is a practical case scenario of enhancing genetic medicine in Africa.

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

Cited by 24 publications

References 23 publications

Increased risk of aminoglycoside-induced hearing loss in MDR-TB patients with HIV coinfection

Increased risk of aminoglycoside-induced hearing loss in MDR-TB patients with HIV coinfection

A known mutation in GJB6 in a large Chinese family with hidrotic ectodermal dysplasia

Enhancing Genetic Medicine: Rapid and Cost-Effective Molecular Diagnosis for a GJB2 Founder Mutation for Hearing Impairment in Ghana

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