[Hearing phenotype and genotypic characteristics in GSDME-related deafness pedigrees].

This retrospective study analyzed three GSDME-related deafness pedigrees diagnosed at the Chinese PLA General Hospital between January 2014 and December 2020. Through whole-exome sequencing and Sanger sequencing validation, all three pedigrees were found to carry splice-site variants causing exon 8 skipping. The patients presented with bilateral, symmetrical, and progressive sensorineural hearing loss, with an age of onset ranging from five to 25 years. The hearing loss initially affected high frequencies and gradually progressed to involve all frequencies. Significant phenotypic heterogeneity was observed, even within the same pedigree, with notable variations in the age of onset and progression rate among individuals carrying the same mutation. A review of the literature indicated that 15 GSDME-caused deafness variants have been reported globally, predominantly clustered around exon 8. This study further confirms that GSDME-related deafness has specific pathogenic mechanisms and significant phenotypic heterogeneity.