在一个越南食指多指畸形血统中发现了一个位于 GLI3 基因锌指结构域内的新型错义变体。

IF 1.5 4区 医学 Q4 GENETICS & HEREDITY
Thy Ngoc Nguyen, Giang Son Tran, Hai Duc Hoang, Long Giang Nguyen
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引用次数: 0

摘要

背景:多指畸形,尤其是食指多指畸形,仍然是一种令人困惑的异常现象,目前还没有特定的基因或基因位点与这种表型有明确的联系。在本研究中,我们对一个食指多指症三代家族进行了调查:方法:对患者进行外显子组测序,筛选出潜在的因果变异。结果:外显子组分析发现了一个新的杂合变异:结果:外显子组分析发现了一个新型杂合子错义变异(c.1482A>T; p.Gln494His),该变异位于该患者和所有受影响家庭成员体内的 GLI3 蛋白锌指 DNA 结合域。值得注意的是,该变异在血统中未受影响的个体中并不存在,这突显了它与多指畸形表型的关联。计算分析表明,GLI3 p.Gln494His影响了一个在不同物种中高度保守的残基:结论:GLI3 锌指 DNA 结合区是音速刺猬信号通路的重要组成部分,通过调控靶基因表达协调胚胎发育的关键环节。这项新发现不仅有助于深入了解胚胎发育过程中多指畸形的分子通路,还有可能提高临床诊断和筛查多指畸形的能力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
A novel missense variant located within the zinc finger domain of the GLI3 gene was identified in a Vietnamese pedigree with index finger polydactyly.

Background: Polydactyly, particularly of the index finger, remains an intriguing anomaly for which no specific gene or locus has been definitively linked to this phenotype. In this study, we conducted an investigation of a three-generation family displaying index finger polydactyly.

Methods: Exome sequencing was conducted on the patient, with a filtration to identify potential causal variation. Validation of the obtained variant was conducted by Sanger sequencing, encompassing all family members.

Results: Exome analysis uncovered a novel heterozygous missense variant (c.1482A>T; p.Gln494His) at the zinc finger DNA-binding domain of the GLI3 protein within the proband and all affected family members. Remarkably, the variant was absent in unaffected individuals within the pedigree, underscoring its association with the polydactyly phenotype. Computational analyses revealed that GLI3 p.Gln494His impacts a residue that is highly conserved across species.

Conclusion: The GLI3 zinc finger DNA-binding region is an essential part of the Sonic hedgehog signaling pathway, orchestrating crucial aspects of embryonic development through the regulation of target gene expression. This novel finding not only contributes valuable insights into the molecular pathways governing polydactyly during embryonic development but also has the potential to enhance diagnostic and screening capabilities for this condition in clinical settings.

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来源期刊
Molecular Genetics & Genomic Medicine
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.
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