title: A Genomic and Protein-Protein Interaction Analyses of Nonsyndromic Hearing Impairment in Cameroon Using Targeted Genomic Enrichment and Massively Parallel Sequencing.
abstract: Hearing impairment (HI) is one of the leading causes of disability in the world, impacting the social, economic, and psychological well-being of the affected individual. This is particularly true in sub-Saharan Africa, which carries one of the highest burdens of this condition. Despite this, there are limited data on the most prevalent genes or mutations that cause HI among sub-Saharan Africans. Next-generation technologies, such as targeted genomic enrichment and massively parallel sequencing, offer new promise in this context. This study reports, for the first time to the best of our knowledge, on the prevalence of novel mutations identified through a platform of 116 HI genes (OtoSCOPE®), among 82 African probands with HI. Only variants OTOF NM_194248.2:c.766-2A>G and MYO7A NM_000260.3:c.1996C>T, p.Arg666Stop were found in 3 (3.7%) and 5 (6.1%) patients, respectively. In addition and uniquely, the analysis of protein-protein interactions (PPI), through interrogation of gene subnetworks, using a custom script and two databases (Enrichr and PANTHER), and an algorithm in the igraph package of R, identified the enrichment of sensory perception and mechanical stimulus biological processes, and the most significant molecular functions of these variants pertained to binding or structural activity. Furthermore, 10 genes (MYO7A, MYO6, KCTD3, NUMA1, MYH9, KCNQ1, UBC, DIAPH1, PSMC2, and RDX) were identified as significant hubs within the subnetworks. Results reveal that the novel variants identified among familial cases of HI in Cameroon are not common, and PPI analysis has highlighted the role of 10 genes, potentially important in understanding HI genomics among Africans.
authors.affiliation: 1 Division of Human Genetics, Department of Pathology, Faculty of Health Sciences - University of Cape Town , Cap Town, South Africa .
authors.forename: Kamogelo
authors.initials: K
authors.lastname: Lebeko
authors.affiliation: 1 Division of Human Genetics, Department of Pathology, Faculty of Health Sciences - University of Cape Town , Cap Town, South Africa .
authors.forename: Noluthando
authors.initials: N
authors.lastname: Manyisa
authors.affiliation: 1 Division of Human Genetics, Department of Pathology, Faculty of Health Sciences - University of Cape Town , Cap Town, South Africa .
authors.forename: Emile R
authors.initials: ER
authors.lastname: Chimusa
authors.affiliation: 2 Division of Computational Biology, Faculty of Health Sciences - University of Cape Town , Cap Town, South Africa .
authors.forename: Nicola
authors.initials: N
authors.lastname: Mulder
authors.affiliation: 1 Division of Human Genetics, Department of Pathology, Faculty of Health Sciences - University of Cape Town , Cap Town, South Africa .
authors.forename: Collet
authors.initials: C
authors.lastname: Dandara
authors.affiliation: 1 Division of Human Genetics, Department of Pathology, Faculty of Health Sciences - University of Cape Town , Cap Town, South Africa .|3 Department of Medicine, Faculty of Health Sciences - University of Cape Town , Cap Town, South Africa .
authors.forename: Ambroise
authors.initials: A
authors.lastname: Wonkam
mesh_terms: D000465:Algorithms; D002163:Cameroon; D003638:Deafness / Q000235:genetics; D023281:Genomics / Q000379:methods*; D034381:Hearing Loss / Q000235:genetics / Q000378:metabolism*; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D011485:Protein Binding
keywords: Africans; Cameroon; genomics; nonsyndromic hearing impairment; protein–protein interaction