Compound heterozygous WNT10A missense variations exacerbated the tooth agenesis caused by hypohidrotic ectodermal dysplasia
© 2024. The Author(s)..
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 β-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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:24 |
|---|---|
| Enthalten in: |
BMC oral health - 24(2024), 1 vom: 27. Jan., Seite 136 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Liu, Yiting [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Development |
|---|
| Anmerkungen: |
Date Completed 29.01.2024 Date Revised 30.01.2024 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1186/s12903-024-03888-5 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM367714027 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM367714027 | ||
| 003 | DE-627 | ||
| 005 | 20240130232206.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240128s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1186/s12903-024-03888-5 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1275.xml |
| 035 | |a (DE-627)NLM367714027 | ||
| 035 | |a (NLM)38280992 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Liu, Yiting |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Compound heterozygous WNT10A missense variations exacerbated the tooth agenesis caused by hypohidrotic ectodermal dysplasia |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 29.01.2024 | ||
| 500 | |a Date Revised 30.01.2024 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2024. The Author(s). | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 β-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 | ||
| 520 | |a CONCLUSIONS: Compound heterozygous WNT10A missense variations may exacerbate the number of missing teeth in HED caused by EDA variation | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Development | |
| 650 | 4 | |a Digenic variations | |
| 650 | 4 | |a EDA | |
| 650 | 4 | |a Hypohidrotic ectodermal dysplasia | |
| 650 | 4 | |a Tooth agenesis | |
| 650 | 4 | |a WNT10A | |
| 650 | 7 | |a WNT10A protein, human |2 NLM | |
| 650 | 7 | |a Wnt Proteins |2 NLM | |
| 700 | 1 | |a Sun, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Caiqi |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Yi |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Siyuan |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Xuechun |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Xiaoshan |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, Qingping |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t BMC oral health |d 2001 |g 24(2024), 1 vom: 27. Jan., Seite 136 |w (DE-627)NLM116714018 |x 1472-6831 |7 nnns |
| 773 | 1 | 8 | |g volume:24 |g year:2024 |g number:1 |g day:27 |g month:01 |g pages:136 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1186/s12903-024-03888-5 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 24 |j 2024 |e 1 |b 27 |c 01 |h 136 | ||