Mutation analysis of the GSDME gene in a Chinese family with non-syndromic hearing loss

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 muta...

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Published in:	PloS one Vol. 17; no. 11; p. e0276233
Main Authors:	Lei, Peiliang, Zhu, Qingwen, Dong, Wenrong, Zhang, Siqi, Sun, Yanyan, Du, Xitong, Geng, Meng, Jiang, Yuan
Format:	Journal Article
Language:	English
Published:	San Francisco Public Library of Science 09-11-2022 Public Library of Science (PLoS)
Subjects:	Age Amino acid metabolism Amino acids Analysis Apoptosis Auditory defects Biology and Life Sciences Care and treatment Cell cycle Deoxyribonucleic acid Development and progression DNA DNA sequencing Gene deletion Gene expression Gene mutations Gene sequencing Gene set enrichment analysis Genetic aspects Genetic factors Genomics Genotypes Health aspects Hearing Hearing loss Medicine and Health Sciences Metabolism Mutation Nervous system Nucleotide sequencing Pathogenesis Pathways Patients People and Places Phenotypes Research and Analysis Methods Signal transduction Signaling Tinnitus Vertigo China Beijing China
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Summary:	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.
Bibliography:	ObjectType-Case Study-2 SourceType-Scholarly Journals-1 ObjectType-Feature-4 content type line 23 ObjectType-Report-1 ObjectType-Article-3 Competing Interests: The authors have declared that no competing interests exist.
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0276233