Identification and Functional Analysis of Novel Mutations in AXIN2 and LRP6 Linked With Non-Syndromic Tooth Agenesis.

IF 1.5 4区医学 Q4 GENETICS & HEREDITY

Molecular Genetics & Genomic Medicine Pub Date : 2025-05-01 DOI:10.1002/mgg3.70101

Wendi Luo, Haitang Yue, Guangtai Song, Jing Cheng, Miao He

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引用次数: 0

Abstract

Background: Tooth agenesis (TA) ranks among the most common dental abnormalities. This study aimed to explore the etiology and pathogenesis in Chinese families with non-syndromic TA.

Methods: Chinese families exhibiting non-syndromic TA were recruited. Exome sequencing was conducted to identify mutations in the candidate genes, followed by Sanger sequencing for validation. Functional studies, including bioinformatics analyses, western blots, and dual-luciferase assays, were performed to analyze the impact of the two mutations on the Wnt/β-catenin pathway.

Results: We identified a novel heterozygous frameshift insertion in AXIN2 [NM_001363813.1: c.1799dupG (p.Asn601GlnfsTer41)] and a novel de novo heterozygous non-frameshift deletion in LRP6 [NM_002336.3: c.3074_3082del (p.1025_1028del)]. Further functional studies indicated that AXIN2 p.Asn601GlnfsTer41 caused hyperactivation of the Wnt/β-catenin pathway, and LRP6 p.1025_1028del led to pathway suppression.

Conclusions: This study expands the spectrum of AXIN2 and LRP6 mutations associated with non-syndromic TA. Our study provided further functional evidence supporting the pathogenicity of suppression and excessive activation of the Wnt signaling pathway in TA.

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与非综合征性牙齿发育相关的AXIN2和LRP6新突变的鉴定和功能分析。

背景：牙齿发育不全是最常见的牙齿异常之一。本研究旨在探讨中国非证型TA家庭的病因及发病机制。方法：招募具有非综合征性TA的中国家庭。外显子组测序确定候选基因的突变，然后进行Sanger测序进行验证。功能研究，包括生物信息学分析、western blots和双荧光素酶检测，分析了这两个突变对Wnt/β-catenin通路的影响。结果：我们在AXIN2中发现了一个新的杂合移码插入[NM_001363813.1: c.1799dupG (p.Asn601GlnfsTer41)]，在LRP6中发现了一个新的新杂合非移码缺失[NM_002336.3: c.3074_3082del (p.1025_1028del)]。进一步的功能研究表明，AXIN2 p.Asn601GlnfsTer41导致Wnt/β-catenin通路过度激活，LRP6 p.1025_1028del导致通路抑制。结论：本研究扩展了与非综合征性TA相关的AXIN2和LRP6突变谱。我们的研究提供了进一步的功能证据，支持Wnt信号通路在TA中的抑制和过度激活的致病性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Genetics & Genomic Medicine Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

4.20

自引率

0.00%

发文量

241

审稿时长

14 weeks

期刊介绍： Molecular Genetics & Genomic Medicine is a peer-reviewed journal for rapid dissemination of quality research related to the dynamically developing areas of human, molecular and medical genetics. The journal publishes original research articles covering findings in phenotypic, molecular, biological, and genomic aspects of genomic variation, inherited disorders and birth defects. The broad publishing spectrum of Molecular Genetics & Genomic Medicine includes rare and common disorders from diagnosis to treatment. Examples of appropriate articles include reports of novel disease genes, functional studies of genetic variants, in-depth genotype-phenotype studies, genomic analysis of inherited disorders, molecular diagnostic methods, medical bioinformatics, ethical, legal, and social implications (ELSI), and approaches to clinical diagnosis. Molecular Genetics & Genomic Medicine provides a scientific home for next generation sequencing studies of rare and common disorders, which will make research in this fascinating area easily and rapidly accessible to the scientific community. This will serve as the basis for translating next generation sequencing studies into individualized diagnostics and therapeutics, for day-to-day medical care. Molecular Genetics & Genomic Medicine publishes original research articles, reviews, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented.