Compound heterozygous WNT10A missense variations exacerbated the tooth agenesis caused by hypohidrotic ectodermal dysplasia
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 seq...
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| Format: | Article |
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BMC
2024-01-01
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| Series: | BMC Oral Health |
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| Online Access: | https://doi.org/10.1186/s12903-024-03888-5 |
| _version_ | 1797276293745606656 |
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| author | Yiting Liu Jing Sun Caiqi Zhang Yi Wu Siyuan Ma Xuechun Li Xiaoshan Wu Qingping Gao |
| author_facet | Yiting Liu Jing Sun Caiqi Zhang Yi Wu Siyuan Ma Xuechun Li Xiaoshan Wu Qingping Gao |
| author_sort | Yiting Liu |
| collection | DOAJ |
| description | 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 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. |
| first_indexed | 2024-03-07T15:26:10Z |
| format | Article |
| id | doaj.art-d24b7f9339064e929531dc3e2455c5b4 |
| institution | Directory Open Access Journal |
| issn | 1472-6831 |
| language | English |
| last_indexed | 2024-03-07T15:26:10Z |
| publishDate | 2024-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Oral Health |
| spelling | doaj.art-d24b7f9339064e929531dc3e2455c5b42024-03-05T17:07:30ZengBMCBMC Oral Health1472-68312024-01-0124111210.1186/s12903-024-03888-5Compound heterozygous WNT10A missense variations exacerbated the tooth agenesis caused by hypohidrotic ectodermal dysplasiaYiting Liu0Jing Sun1Caiqi Zhang2Yi Wu3Siyuan Ma4Xuechun Li5Xiaoshan Wu6Qingping Gao7The Stomatology Center of Xiangya Hospital, Central South UniversityThe Stomatology Center of Xiangya Hospital, Central South UniversityThe Stomatology Center of Xiangya Hospital, Central South UniversityThe Stomatology Center of Xiangya Hospital, Central South UniversityThe Stomatology Center of Xiangya Hospital, Central South UniversityThe Stomatology Center of Xiangya Hospital, Central South UniversityThe Stomatology Center of Xiangya Hospital, Central South UniversityThe Stomatology Center of Xiangya Hospital, Central South UniversityAbstract 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.https://doi.org/10.1186/s12903-024-03888-5Hypohidrotic ectodermal dysplasiaEDAWNT10ADigenic variationsTooth agenesisDevelopment |
| spellingShingle | Yiting Liu Jing Sun Caiqi Zhang Yi Wu Siyuan Ma Xuechun Li Xiaoshan Wu Qingping Gao Compound heterozygous WNT10A missense variations exacerbated the tooth agenesis caused by hypohidrotic ectodermal dysplasia BMC Oral Health Hypohidrotic ectodermal dysplasia EDA WNT10A Digenic variations Tooth agenesis Development |
| title | Compound heterozygous WNT10A missense variations exacerbated the tooth agenesis caused by hypohidrotic ectodermal dysplasia |
| title_full | Compound heterozygous WNT10A missense variations exacerbated the tooth agenesis caused by hypohidrotic ectodermal dysplasia |
| title_fullStr | Compound heterozygous WNT10A missense variations exacerbated the tooth agenesis caused by hypohidrotic ectodermal dysplasia |
| title_full_unstemmed | Compound heterozygous WNT10A missense variations exacerbated the tooth agenesis caused by hypohidrotic ectodermal dysplasia |
| title_short | Compound heterozygous WNT10A missense variations exacerbated the tooth agenesis caused by hypohidrotic ectodermal dysplasia |
| title_sort | compound heterozygous wnt10a missense variations exacerbated the tooth agenesis caused by hypohidrotic ectodermal dysplasia |
| topic | Hypohidrotic ectodermal dysplasia EDA WNT10A Digenic variations Tooth agenesis Development |
| url | https://doi.org/10.1186/s12903-024-03888-5 |
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