Eight EDA mutations in Chinese patients with tooth agenesis and genotype-phenotype analysis.
Oral Dis
; 2024 Jan 29.
Article
em En
| MEDLINE
| ID: mdl-38287639
ABSTRACT
OBJECTIVE:
Tooth agenesis is a common craniofacial malformation, which is often associated with gene mutations. The purpose of this research was to investigate and uncover ectodysplasin A (EDA) gene variants in eight Chinese families affected with tooth agenesis.METHODS:
Genomic DNA was extracted from tooth agenesis families and sequenced using whole-exome sequencing. The expression of ectodysplasin A1 (EDA1) protein was studied by western blot, binding activity with receptor was tested by pull-down and the NF-κB transcriptional activity was analyzed by Dual luciferase assay.RESULTS:
Eight EDA missense variants were discovered, of which two (c.T812C, c.A1073G) were novel. The bioinformatics analysis indicated that these variants might be pathogenic. The tertiary structure analysis revealed that these eight variants could cause structural damage to EDA proteins. In vitro functional studies demonstrated that the variants greatly affect protein stability or impair the EDA-EDAR interaction; thereby significantly affecting the downstream NF-κb transcriptional activity. In addition, we summarized the genotype-phenotype correlation caused by EDA variants and found that EDA mutations leading to NSTA are mostly missense mutations located in the TNF domain.CONCLUSION:
Our results broaden the variant spectrum of the EDA gene associated with tooth agenesis and provide valuable information for future genetic counseling.
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Base de dados:
MEDLINE
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article