Several causative factors are associated with hearing loss (HL) and brain disorders. However, there are many unidentified disease modifiers in these conditions. Our study summarised the most common brain disorders associated with HL and highlighted mechanisms of pathologies. We searched the literature for published articles on HL and brain disorders. Alzheimer’s disease/dementia, Parkinson’s disease, cognitive impairment, autism spectrum disorder, ataxia, epilepsy, stroke, and hypoxic-ischaemic encephalopathy majorly co-interact with HL. The estimated incidence rate was 113 per 10,000 person-years. Genetic, epigenetic, early life/neonatal stress, hypoxia, inflammation, nitric oxide infiltration, endoplasmic reticulum stress, and excess glutamate were the distinguished modifiers identified. Various mechanisms like adhesion molecules, transport proteins, hair cell apoptosis, and neurodegeneration have been implicated in these conditions and are serving as potential targets for therapies. To improve the quality of life of patients, these understandings will improve clinical diagnoses and management of HL and brain disorders.

Human mouse orthologous hearing impairment genes were investigated in African patients for causal variants. A homozygous mutation in the exon 13 BRCT3 of microcephalin1 (MCPH1) gene was reported in non-syndromic hearing impairment (NSHI). The present study screened multiplex families; ninety (n=90) patients and 106 controls from Cameroon and South Africa. The estimated mode of inheritance was 34.8% autosomal recessive, 34.8% autosomal dominant, 21.74% mitochondrial, and 8.66% X-linked. Four rare missense variants and seven novel variants were identified in the candidate gene (MCPH1). The variants MCPH1 c.2222G>A p.(R741Q) (Alt Allele A=0.0000) and novel homozygous MCPH1 c.2234A>C p.(H745P) were absent in the 106 ethnically matched controls. The evolutionary analyses revealed that the MCPH1 protein evolved in 150 taxa while about 28 condensed in a phylogeny cluster that indicated similar substitution rates, divergent lengths, and positive selections, particularly in the two closest taxa to humans (chimpanzee and gorilla). The protein modelling and surface hydrophobicity analyses suggest a change in atomic charges at the helix-loop that mediates dimerization and DNA binding, such that the wildtype equilibrates at 0.072 nm while the mutant equilibrates at 0.042 nm in-silico. Our study suggests a further understanding of the roles of MCPH1 gene in NSHI using functional assays.