PDF(Pubmed)
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.
CONCLUSIONS: Our finding confirmed the pathogenicity of c.291G >A, thus extending the pathogenic mutation spectrum of F7, and providing insights for effective reproductive counseling.
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.
CONCLUSIONS: Our finding confirmed the pathogenicity of c.291G >A, thus extending the pathogenic mutation spectrum of F7, and providing insights for effective reproductive counseling.
摘要：
背景：由于氨基酸的非取代，同义变体是非致病性的。然而,同义外显子末端核苷酸取代可能影响剪接。剪接变体易于在RNA水平上分析血细胞中表达的基因。小基因分析提供了另一种在外周血中表达不良或不表达的基因的剪接变体分析的方法。
方法：进行全外显子组测序以筛选先证者中潜在的致病性突变，通过Sanger测序在家族中验证。使用小基因技术分析同义突变的致病性。
结果：先证者在F7中包含复合异质变体c。[291G>A;572-50C>T]和c.6811G>T，其中同义变体c.291G>A位于外显子3的末端位置。小基因分析显示，由于这种突变，外显子3跳跃，可能会影响蛋白质序列，结构,和功能。
结论：我们的发现证实了c.291G>A的致病性，从而扩展F7的致病突变谱,为有效的生殖咨询提供见解。
方法：进行全外显子组测序以筛选先证者中潜在的致病性突变，通过Sanger测序在家族中验证。使用小基因技术分析同义突变的致病性。
结果：先证者在F7中包含复合异质变体c。[291G>A;572-50C>T]和c.6811G>T，其中同义变体c.291G>A位于外显子3的末端位置。小基因分析显示，由于这种突变，外显子3跳跃，可能会影响蛋白质序列，结构,和功能。
结论：我们的发现证实了c.291G>A的致病性，从而扩展F7的致病突变谱,为有效的生殖咨询提供见解。
