Targeted genetic sreening for pathogenic mutations in House-Mouse orthologs genes. House-Mouse Hearing Impairment Genes Studies

The prominent hearing impairment (HI) genes are GJB2 and GJB6. Identified HI mutations only account for most cases in the European and Asian populations. There is a low pickup rate of these mutations in African populations. Recently, we performed a whole-exome sequencing analysis and analysed 34 novel human-mouse orthologous HI genes in African cohorts, these genes were initially reported in mouse studies. Our study identified a homozygous mutation in the Microcephalin (MCPH1) gene in human studies. The MCPH1 is a DNA damage response protein involved in the regulation of CHK1 and BRCA1. It has been implicated in chromosome condensation and DNA damage-induced cellular responses. It may play a role in neurogenesis by coordinating the cell cycle and the centrosome cycle 14. The human MCPH1 gene contains 14 coding exons. The BRCT1 domain comprising exon 1 – 4 of the MCPH1 has been the hotspot for causative mutations associated with primary microcephaly. However, our study was the first to identify a mutation in the BRCT2 (exon 13) domain of this gene associated with the HI study. Therefore, the aim of the present study is to investigate the evolution of MCPH1 and screen the BRCT2 domain in patients and controls diagnosed with NSHI.