Minigene assay for verifying the splicing effects of the rare variants in the SLC12A2 gene at c.2930-1G>a.

IF 1.2 4区 医学 Q3 OTORHINOLARYNGOLOGY
Lin Mengsi, Zhu Qingwen, Cui Aimin, Wang Jing
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引用次数: 0

Abstract

Background: Hearing loss (HL) is a prevalent sensory impairment with a genetic basis. The SLC12A2 gene, encoding NKCC1, is vital for inner ear ion balance. The c.2930-1G > A variant is a novel mutation potentially linked to sensorineural hearing loss.

Objectives: To investigate the splicing and protein expression effects of the c.2930-1G>A variant in SLC12A2 and its role in hearing loss.

Material and methods: Minigene assays and plasmid transfection in HEK-293T and Hela cells were used to study splicing. Protein expression and modification were also assessed.

Results: The c.2930-1G>A variant caused partial exon skipping, altering mRNA splicing in both cell types. This suggests a potential involvement in sensorineural hearing loss. Protein analysis showed the E21del mutation increased expression without altering modification patterns, whereas the 2930_2977del mutation reduced both, possibly impacting stability or modification sites.

Conclusions and significance: The c.2930-1G>A variant likely contribute to hearing loss by disrupting splicing and protein expression. Currently a Variant of Uncertain Significance (VUS), its pathogenicity is supported by these findings. Further research is needed to confirm its role, emphasizing the need for integrated genetic and clinical data in auditory disorders management.

背景:听力损失(HL)是一种普遍存在的感官损伤,具有遗传基础。编码 NKCC1 的 SLC12A2 基因对内耳离子平衡至关重要。c.2930-1G > A 变异是一种新型突变,可能与感音神经性听力损失有关:研究SLC12A2中c.2930-1G>A变体的剪接和蛋白表达效应及其在听力损失中的作用:材料和方法:使用微型基因测定和质粒转染 HEK-293T 和 Hela 细胞来研究剪接。结果结果:c.2930-1G>A 变体导致部分外显子跳过,改变了两种细胞中的 mRNA 剪接。这表明该基因可能与感音神经性听力损失有关。蛋白质分析表明,E21del 突变增加了表达,但没有改变修饰模式,而 2930_2977del 突变则减少了表达,可能影响了稳定性或修饰位点:c.2930-1G>A变异可能通过破坏剪接和蛋白质表达导致听力损失。该变异目前是一个意义不明的变异(VUS),其致病性得到了这些研究结果的支持。要确认其作用还需要进一步的研究,这也强调了在听觉障碍管理中整合遗传和临床数据的必要性。
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来源期刊
Acta Oto-Laryngologica
Acta Oto-Laryngologica 医学-耳鼻喉科学
CiteScore
2.50
自引率
0.00%
发文量
99
审稿时长
3-6 weeks
期刊介绍: Acta Oto-Laryngologica is a truly international journal for translational otolaryngology and head- and neck surgery. The journal presents cutting-edge papers on clinical practice, clinical research and basic sciences. Acta also bridges the gap between clinical and basic research.
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