Compound heterozygous WNT10A missense variations exacerbated the tooth agenesis caused by hypohidrotic ectodermal dysplasia.
BMC Oral Health
; 24(1): 136, 2024 Jan 27.
Article
en En
| MEDLINE
| ID: mdl-38280992
ABSTRACT
BACKGROUND:
The aim of this study was to analyse the differences in the phenotypes of missing teeth between a pair of brothers with hypohidrotic ectodermal dysplasia (HED) and to investigate the underlying mechanism by comparing the mutated gene loci between the brothers with whole-exome sequencing.METHODS:
The clinical data of the patients and their mother were collected, and genomic DNA was extracted from peripheral blood samples. By Whole-exome sequencing filtered for a minor allele frequency (MAF) ≤0.05 non-synonymous single-nucleotide variations and insertions/deletions variations in genes previously associated with tooth agenesis, and variations considered as potentially pathogenic were assessed by SIFT, Polyphen-2, CADD and ACMG. Sanger sequencing was performed to detect gene variations. The secondary and tertiary structures of the mutated proteins were predicted by PsiPred 4.0 and AlphaFold 2.RESULTS:
Both brothers were clinically diagnosed with HED, but the younger brother had more teeth than the elder brother. An EDA variation (c.878 T > G) was identified in both brothers. Additionally, compound heterozygous variations of WNT10A (c.511C > T and c.637G > A) were identified in the elder brother. Digenic variations in EDA (c.878 T > G) and WNT10A (c.511C > T and c.637G > A) in the same patient have not been reported previously. The secondary structure of the variant WNT10A protein showed changes in the number and position of α-helices and ß-folds compared to the wild-type protein. The tertiary structure of the WNT10A variant and molecular simulation docking showed that the site and direction where WNT10A binds to FZD5 was changed.CONCLUSIONS:
Compound heterozygous WNT10A missense variations may exacerbate the number of missing teeth in HED caused by EDA variation.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Diente
/
Displasia Ectodérmica
/
Displasia Ectodermal Anhidrótica Tipo 1
/
Anodoncia
Tipo de estudio:
Prognostic_studies
Límite:
Humans
/
Male
Idioma:
En
Revista:
BMC Oral Health
Asunto de la revista:
ODONTOLOGIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
China