遗传决定性听力神经病谱系障碍的异质组
Anastasiia A Buianova1, Marina V Bazanova2, Vera A Belova1
1The Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Pirogov Russian National Research Medical University, 117513 Moscow, Russia.
International journal of molecular sciences
|December 17, 2024
概括
听力神经病谱系障碍 (ANSD) 经常被误诊,影响10%的听力障碍. 基因测试在ANSD患者中发现了变异,与感觉神经听力损失 (SNHL) 患者不同,揭示了明显的听力学和父母满意度差异.
科学领域:
- 遗传学和听力学
- 儿科听力障碍 儿童听力障碍
- 分子诊断学 分子诊断
背景情况:
- 听力神经病谱障碍 (ANSD) 是一种复杂的听力障碍,通常在标准测试中错过.
- 它占儿科听力损失的10%左右,并且经常与遗传因素有关.
- 区分ANSD与感觉神经听力损失 (SNHL) 对于适当的管理至关重要.
研究的目的:
- 为了研究儿童ANSD的遗传基础.
- 为了比较ANSD和SNHL之间的听觉特征和家长满意度.
- 为了确定ANSD的潜在诊断标记.
主要方法:
- 评估了122名有听力障碍的儿童 (102名SNHL,20名ANSD).
- 用qPCR.使用GJB2变异的基因型SNHL患者.
- 在ANSD患者身上进行了整体外基因组测序,分析了249个基因的变异.
- 进行过渡唤起的音声发射 (TEOAEs) 和听觉稳定状态响应 (ASSR) 测试.
- 管理了一个调查问卷,以评估父母的生活质量和满意度.
主要成果:
- 在54.9%的SNHL患者中发现 homozygous GJB2 变体.
- 在60%的ANSD患者中检测到遗传变异,包括OTOF,CDH23,TMC1,COL11A1,PRPS1,TWNK和HOMER2.2中的新型变异.
- 在ANSD和SNHL组之间,TEOAEs在4000Hz时显示出显著的差异 (p = 0.0084).
- 与ANSD患者的PTA相比,ASSR在500 Hz (p = 2.69 × 10^-4) 和1000 Hz (p = 0.0255) 显示出显著的差异.
- 与SNHL儿童相比,ANSD儿童的父母报告了更大的不确定性和更低的满意度 (p = 0.0026).
结论:
- 基因分析对于诊断ANSD至关重要,与SNHL相比,它揭示了不同的遗传特征.
- 像ASSR这样的听力学测试在ANSD患者中显示出与PTA的显著差异.
- 父母对ANSD的不确定性和较低的满意度凸显了改善诊断清晰度和支持的需要.
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