Children’s Nutrition Research Center Staff Publications
Language
English
Publication Date
1-1-2024
Journal
Journal of Cellular and Molecular Medicine
DOI
10.1111/jcmm.18004
PMID
37864300
PMCID
PMC10805510
PubMedCentral® Posted Date
10-20-2023
PubMedCentral® Full Text Version
Post-print
Abstract
Nonsyndromic hearing loss (NSHL) is a genetically diverse, highly heterogeneous condition characterised by deafness, and Gasdermin E (GSDME) variants have been identified as directly inducing autosomal dominant NSHL. While many NSHL cases associated with GSDME involve the skipping of exon 8, there is another, less understood pathogenic insertion variant specifically found in Chinese pedigrees that causes deafness, known as autosomal dominant 5 (DFNA5) hearing loss. In this study, we recruited a large Chinese pedigree, conducted whole‐exome and Sanger sequencing to serve as a comprehensive clinical examination, and extracted genomic DNA samples for co‐segregation analysis of the members. Conservation and expression analyses for GSDME were also conducted. Our clinical examinations revealed an autosomal dominant phenotype of hearing loss in the family. Genetic analysis identified a novel insertion variant in GSDME exon 8 (GSDME: NM_004403.3: c.1113_1114insGGGGTGCAGCTTACAGGGTGGGTGT: p. P372fs*36). This variant is segregated with the deafness phenotype of this pedigree. The GSDME gene was highly conserved in the different species we analysed, and its mRNA expression was ubiquitously low in different human tissues. In conclusion, we have successfully identified a novel pathogenic insertion variant of GSDME in a Chinese pedigree that causes deafness, shedding light on the genetic basis of hearing loss within this specific family. Our findings expand the spectrum of known variants associated with GSDME‐related deafness and may further support both the underlying gain‐of‐function mechanism and functional associations of GSDME hearing loss variants.
Keywords
Humans, Pedigree, Hearing Loss, Deafness, China, Mutation, Hearing Loss, Sensorineural, genetics, GSDME, nonsyndromic hearing loss (NSHL), variant, whole‐exome sequencing (WES)
Published Open-Access
yes
Recommended Citation
Cheng, Jingliang; Li, Ting; Tan, Qi; et al., "Novel, Pathogenic Insertion Variant of Gsdme Associates With Autosomal Dominant Hearing Loss in a Large Chinese Pedigree" (2024). Children’s Nutrition Research Center Staff Publications. 280.
https://digitalcommons.library.tmc.edu/staff_pub/280
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