Abstract：
OBJECTIVE: ACAN gene variants, prevalent monogenic defects linked to short stature, are characterized by impaired cartilage generation in growth plates. We aimed to unravel the genetic basis of short stature in a specific pedigree by investigating the role of a novel non-canonical splicing-site variant, c.630-13G > A, within the ACAN gene.
METHODS: Sanger sequencing was used for pedigree verification, and the effects of this variant on mRNA splicing were analyzed through minigene assay.
RESULTS: The study revealed that this variant led to the creation of a previously unreported splice site in the fourth intron, resulting in the incorporation of an 11 bp sequence from the intron into the final transcript. This alteration led to a frameshift and formation of a premature termination codon, impacting the structure of the aggrecan protein.
CONCLUSIONS: We document the pathogenicity of an ACAN non-canonical splicing-site variant, emphasizing the significance of considering intronic variants during genetic testing.
METHODS: Sanger sequencing was used for pedigree verification, and the effects of this variant on mRNA splicing were analyzed through minigene assay.
RESULTS: The study revealed that this variant led to the creation of a previously unreported splice site in the fourth intron, resulting in the incorporation of an 11 bp sequence from the intron into the final transcript. This alteration led to a frameshift and formation of a premature termination codon, impacting the structure of the aggrecan protein.
CONCLUSIONS: We document the pathogenicity of an ACAN non-canonical splicing-site variant, emphasizing the significance of considering intronic variants during genetic testing.
摘要：
目的：ACAN基因变异，普遍的单基因缺陷与身材矮小有关，以生长板中软骨生成受损为特征。我们旨在通过研究一种新的非经典剪接位点变体的作用来揭示特定谱系中身材矮小的遗传基础。c.630-13G>A，在ACAN基因内。
方法：使用Sanger测序进行系谱验证，并通过小基因分析分析了该变体对mRNA剪接的影响。
结果：研究表明，该变体导致在第四个内含子中产生了以前未报道的剪接位点，导致来自内含子的11bp序列掺入到最终的转录物中。这种改变导致移码和过早终止密码子的形成，影响聚集蛋白聚糖蛋白的结构。
结论：我们记录了ACAN非规范剪接位点变体的致病性，强调在基因测试中考虑内含子变异的重要性。
方法：使用Sanger测序进行系谱验证，并通过小基因分析分析了该变体对mRNA剪接的影响。
结果：研究表明，该变体导致在第四个内含子中产生了以前未报道的剪接位点，导致来自内含子的11bp序列掺入到最终的转录物中。这种改变导致移码和过早终止密码子的形成，影响聚集蛋白聚糖蛋白的结构。
结论：我们记录了ACAN非规范剪接位点变体的致病性，强调在基因测试中考虑内含子变异的重要性。
