No abstract

Background Hearing loss is considered one of the most common sensory nervous system defects, about 60% of which are caused by genetic factors. Mutations in the GSDME gene are responsible for post-lingual, progressive, autosomal dominant hearing loss. This study aimed to characterize the genetic mutations and clinical features of a Chinese GSDME family. Methods After clinical evaluations, high-throughput DNA sequencing was conducted using DNA samples from this family. Sanger sequencing was performed to verify the suspected variants. A detailed genotype and phenotype analysis were carried out. Gene set enrichment analysis (GSEA) was performed to identify the signaling pathway associated with GSDME expression. Results A known hotspot heterozygous splice-site variation (c.991-15_991_13delTTC) was identified and shown to segregate with the hearing loss phenotype in the family. This pathogenic splice-site variant results in skipping of exon 8. GSEA analysis identified changes in regulation of the cell cycle checkpoint, peroxisome, and amino acid metabolism signaling pathways. Conclusions We identified a reported mutation in the GSDME gene. Our findings support the 3 bp deletion (c.991-15_991-13del) was a hotspot variation, and it emerged as an essential contributor to autosomal dominant progressive hearing loss in East Asians. GSDME gene is closely associated with a range of signaling pathways. These characterized findings may provide new evidence for pathogenesis.