Synonymous variant at the terminal nucleotide in exon 3 of F7 causes abnormal splicing: A case report.

IF 1.5 4区医学 Q4 GENETICS & HEREDITY Molecular Genetics & Genomic Medicine Pub Date : 2024-07-01 DOI:10.1002/mgg3.2492

Liya Wang, Wenshan Zeng, Yeqing Qian, Yixi Sun, Min Chen, Bei Liu, Junjie Hu, Ping Yu, Minyue Dong

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Abstract

Background: Synonymous variants are non-pathogenic due to non-substitution of amino acids. However, synonymous exonic terminal nucleotide substitutions may affect splicing. Splicing variants are easily analyzed at RNA level for genes expressed in blood cells. Minigene analysis provides another method for splicing variant analysis of genes that are poorly or not expressed in peripheral blood.

Methods: Whole exome sequencing was performed to screen for potential pathogenic mutations in the proband, which were validated within the family by Sanger sequencing. The pathogenicity of the synonymous mutation was analyzed using the minigene technology.

Results: The proband harbored the compound heterogeneous variants c. [291G >A; 572-50C >T] and c.681 + 1G >T in F7, of which the synonymous variant c.291G >A was located at the terminal position of exon 3. Minigene analysis revealed exon3 skipping due to this mutation, which may have subsequently affected protein sequence, structure, and function.

Conclusion: Our finding confirmed the pathogenicity of c.291G >A, thus extending the pathogenic mutation spectrum of F7, and providing insights for effective reproductive counseling.

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F7 第 3 外显子末端核苷酸的同义变异导致剪接异常：病例报告

背景：同义变异由于不替换氨基酸而不致病。然而，同义外显子末端核苷酸替换可能会影响剪接。对于在血细胞中表达的基因，剪接变异很容易在 RNA 水平上进行分析。微型基因分析为剪接变异分析提供了另一种方法，可用于分析外周血中表达较少或不表达的基因：方法：进行了全外显子组测序，以筛查潜在的致病基因突变，并通过桑格测序在家族内部进行了验证。利用微型基因技术分析了同义突变的致病性：结果：该患者在 F7 中携带有 c. [291G >A; 572-50C >T] 和 c.681 + 1G >T 的复合异质性变异，其中同义变异 c.291G >A 位于第 3 号外显子的末端位置。迷你基因分析表明，该突变导致了第3外显子的缺失，随后可能会影响蛋白质的序列、结构和功能：我们的发现证实了 c.291G >A 的致病性，从而扩展了 F7 的致病突变谱，并为有效的生殖咨询提供了启示。

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.