Expanding the phenotypic spectrum in ESRRB related sensorineural hearing loss: Evidence provided via detecting novel nonsense mutation in an Egyptian family

Abstract

Autosomal recessive non-syndromic hearing loss (ARNSHL) is very heterogeneous at the molecular level with ˃75 genes being involved. In this study, whole exome sequencing (WES) was applied to investigate the molecular defect in an Egyptian male child with sensorineural hearing loss. The patient also exhibited mild neurological and overt orodental abnormalities. Novel nonsense mutation (p.Arg187*) in the ESRRB gene has been detected resulting in early protein truncation. ESRRB gene is coding for a transcription factor involved in the development of the inner ear. About two decades ago, ESRRB gene mutations were defined as a relatively rare cause of non-syndromic hearing loss. This case represented the first Egyptian patient to be reported with a genetic variation in the ESRRB gene extending the clinical phenotype related to ESRRB variants. Further information about gene expression pattern and molecular pathways as well as possible interplay between the manifested neurological symptoms would support the role of ESRRB gene in development of the patient's phenotypic presentation. On the other hand, this study provided an example for the favorable output of comprehensive molecular screening approaches in expanding the phenotypic spectrum of previously described genes.