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Dose Dependence Effect in Biallelic WNT10A Variant-Associated Tooth Agenesis Phenotype
The goal of this study was to identify the pathogenic gene variants in patients with odonto-onycho-dermal dysplasia syndrome (OODD) or nonsyndromic tooth agenesis. Four unrelated individuals with tooth agenesis and their available family members were recruited. Peripheral blood was collected from fo...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9776737/ https://www.ncbi.nlm.nih.gov/pubmed/36553094 http://dx.doi.org/10.3390/diagnostics12123087 |
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author | Liu, Haochen Lin, Bichen Liu, Hangbo Su, Lanxin Feng, Hailan Liu, Yang Yu, Miao Han, Dong |
author_facet | Liu, Haochen Lin, Bichen Liu, Hangbo Su, Lanxin Feng, Hailan Liu, Yang Yu, Miao Han, Dong |
author_sort | Liu, Haochen |
collection | PubMed |
description | The goal of this study was to identify the pathogenic gene variants in patients with odonto-onycho-dermal dysplasia syndrome (OODD) or nonsyndromic tooth agenesis. Four unrelated individuals with tooth agenesis and their available family members were recruited. Peripheral blood was collected from four probands and five family members. Whole-exome sequencing (WES) and Sanger sequencing were used to identify the pathogenic gene variants. The harmfulness of these variations was predicted by bioinformatics. We identified four biallelic variants of the WNT10A gene in four patients, respectively: the proband#660: c.1176C > A (p.Cys392*) and c.812G > A (p.Cys271Tyr); the proband#681: c.637G > A (p.Gly213Ser) and c.985C > T (p.Arg329*); the proband#829: c.511C > T (p.Arg171Cys) and c.637G > A (p.Gly213Ser); and the proband#338: c.926A> G (p.Gln309Arg) and c.511C > T (p.Arg171Cys). Among them, two variants (c.812G > A; p.Cys271Tyr and c.985C > T; p.Arg329*) were previously unreported. Bioinformatics analysis showed that the pathogenicity of these six variants was different. Tertiary structure analysis showed that these variants were predicted to cause structural damage to the WNT10A protein. Genotype–phenotype analysis showed that the biallelic variants with more harmful effects, such as nonsense variants, caused OODD syndrome (#660 Ⅱ-1) or severe nonsyndromic tooth agenesis (NSTA) (#681 Ⅱ-1); the biallelic variants with less harmful effects, such as missense variants, caused a mild form of NSTA (#829 Ⅱ-2 and #338 Ⅱ-1). Individuals with a heterozygous variant presented a mild form of NSTA or a normal state. Our results further suggest the existence of the dose dependence of WNT10A pathogenicity on the tooth agenesis pattern, which broadens the variation spectrum and phenotype spectrum of WNT10A and could help with clinical diagnosis, treatment, and genetic counseling. |
format | Online Article Text |
id | pubmed-9776737 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-97767372022-12-23 Dose Dependence Effect in Biallelic WNT10A Variant-Associated Tooth Agenesis Phenotype Liu, Haochen Lin, Bichen Liu, Hangbo Su, Lanxin Feng, Hailan Liu, Yang Yu, Miao Han, Dong Diagnostics (Basel) Article The goal of this study was to identify the pathogenic gene variants in patients with odonto-onycho-dermal dysplasia syndrome (OODD) or nonsyndromic tooth agenesis. Four unrelated individuals with tooth agenesis and their available family members were recruited. Peripheral blood was collected from four probands and five family members. Whole-exome sequencing (WES) and Sanger sequencing were used to identify the pathogenic gene variants. The harmfulness of these variations was predicted by bioinformatics. We identified four biallelic variants of the WNT10A gene in four patients, respectively: the proband#660: c.1176C > A (p.Cys392*) and c.812G > A (p.Cys271Tyr); the proband#681: c.637G > A (p.Gly213Ser) and c.985C > T (p.Arg329*); the proband#829: c.511C > T (p.Arg171Cys) and c.637G > A (p.Gly213Ser); and the proband#338: c.926A> G (p.Gln309Arg) and c.511C > T (p.Arg171Cys). Among them, two variants (c.812G > A; p.Cys271Tyr and c.985C > T; p.Arg329*) were previously unreported. Bioinformatics analysis showed that the pathogenicity of these six variants was different. Tertiary structure analysis showed that these variants were predicted to cause structural damage to the WNT10A protein. Genotype–phenotype analysis showed that the biallelic variants with more harmful effects, such as nonsense variants, caused OODD syndrome (#660 Ⅱ-1) or severe nonsyndromic tooth agenesis (NSTA) (#681 Ⅱ-1); the biallelic variants with less harmful effects, such as missense variants, caused a mild form of NSTA (#829 Ⅱ-2 and #338 Ⅱ-1). Individuals with a heterozygous variant presented a mild form of NSTA or a normal state. Our results further suggest the existence of the dose dependence of WNT10A pathogenicity on the tooth agenesis pattern, which broadens the variation spectrum and phenotype spectrum of WNT10A and could help with clinical diagnosis, treatment, and genetic counseling. MDPI 2022-12-07 /pmc/articles/PMC9776737/ /pubmed/36553094 http://dx.doi.org/10.3390/diagnostics12123087 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Liu, Haochen Lin, Bichen Liu, Hangbo Su, Lanxin Feng, Hailan Liu, Yang Yu, Miao Han, Dong Dose Dependence Effect in Biallelic WNT10A Variant-Associated Tooth Agenesis Phenotype |
title | Dose Dependence Effect in Biallelic WNT10A Variant-Associated Tooth Agenesis Phenotype |
title_full | Dose Dependence Effect in Biallelic WNT10A Variant-Associated Tooth Agenesis Phenotype |
title_fullStr | Dose Dependence Effect in Biallelic WNT10A Variant-Associated Tooth Agenesis Phenotype |
title_full_unstemmed | Dose Dependence Effect in Biallelic WNT10A Variant-Associated Tooth Agenesis Phenotype |
title_short | Dose Dependence Effect in Biallelic WNT10A Variant-Associated Tooth Agenesis Phenotype |
title_sort | dose dependence effect in biallelic wnt10a variant-associated tooth agenesis phenotype |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9776737/ https://www.ncbi.nlm.nih.gov/pubmed/36553094 http://dx.doi.org/10.3390/diagnostics12123087 |
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