Novel GRHL2 Gene Variant Associated with Hearing Loss: A Case Report and Review of the Literature

Abstract

In contrast to the recessive form, hearing loss inherited in a dominant manner is more often post-lingual and typically results in a progressive sensorineural hearing loss with variable severity and late onset. Variants in the GRHL2 gene are an extremely rare cause of dominantly inherited hearing loss. Genetic testing is a crucial part of the identification of the etiology of hearing loss in individual patients, especially when performed with next-generation sequencing, enabling simultaneous analysis of numerous genes, including those rarely associated with hearing loss. We aimed to evaluate the genetic etiology of hearing loss in a family with moderate late-onset hearing loss using next-generation sequencing and to conduct a review of reported variants in the GRHL2 gene. We identified a novel disease-causing variant in the GRHL2 gene (NM_024915: c.1510C>T; p.Arg504Ter) in both affected members of the family. They both presented with moderate late-onset hearing loss with no additional clinical characteristics. Reviewing known GRHL2 variants associated with hearing loss, we can conclude that they are more likely to be truncating variants, while the associated onset of hearing loss is variable.

Clinical and genome-wide association analysis of chemoradiation-induced hearing loss in nasopharyngeal carcinoma

“…GRHL2 gene encodes a transcription factor involved in epithelial differentiation, morphogenesis, and maintenance (Werth et al 2010 ). Mutations in this gene, usually truncating variants, have been reported to cause autosomal dominant non-syndromic hearing loss (Peters et al 2002 ; Vona et al 2013 ; Trebusak Podkrajsek et al 2021 ). Grhl2 protein deficiency in a zebrafish model directly reduced the expression of cldnb and epcam, junction proteins in otic epithelial cells, resulting in abnormal development of the inner ear and impaired hearing (Han et al 2011 ).…”