PloS one · 2022
Mutation analysis of the GSDME gene in a Chinese family with non-syndromic hearing loss.
Клинический случайСтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Lei Peiliang, Zhu Qingwen, Dong Wenrong, Zhang Siqi, Sun Yanyan, Du Xitong, Geng Meng, Jiang Yuan
Аннотация
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.
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.