The natural history of the relationship between OTOF mutation-related genotypes and audiological phenotypes
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摘要: 听力损失是最常见的感觉障碍之一。近年来，由OTOF基因突变引起的听神经病谱系障碍受到了国内外学者的广泛关注。OTOF基因是国际上第一个在基因治疗方面取得突破的耳聋相关基因。携带OTOF基因突变的患者多表现为先天性或语前发病的重度至极重度听力损失，而少数患者则可能表现为轻至中度或进行性听力损失以及对温度敏感的听力损失。本文综合分析了国内外关于OTOF基因突变病例的报道，深入探讨了OTOF基因型与表型之间的关系，并重点分析了在中国人群中的自然病史特点。本综述旨在为OTOF基因突变相关听力损失的临床诊断、评估和治疗提供参考。Abstract: Sensorineural hearing loss is one of the most common sensory disorders. In recent years, auditory neuropathy spectrum disorders caused by mutations in the OTOF gene have garnered significant attention worldwide, marking it as the first deafness gene with breakthroughs in gene therapy. Most patients with OTOF gene mutations present with stable, congenital, or prelingual onset of hearing loss, which can range from severe to profound and even complete hearing loss. However, a minority of patients may exhibit mild to moderate progressive hearing loss or temperature-sensitive hearing loss. This review further explores the genotype-phenotype relationship of the OTOF gene based on reported cases in China and abroad. Additionally, we analyze the characteristics of the natural history of OTOFgene mutations within the Chinese population. This study aims to provide a reference for the clinical diagnosis, evaluation, and treatment of hearing loss associated with OTOF gene mutations.
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Key words:
- hearing loss /
- hereditary /
- OTOF gene /
- auditory neuropathy
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图 1 中国患者的OTOF基因突变谱(上方为截断或剪切突变，下方为非截断突变；转录本：NM_001287489.2；结构域信息参考
https://www.ncbi.nlm.nih.gov/gene/9381 )表 1 温度敏感性听神经病的OTOF突变及听力表型
DNA突变 氨基酸突变 非发热时听力 发热时听力 期刊作者(参考文献) c.1544T>C p.I515T 轻度听力损失 轻度/极重度听力损失 Strenzke等(2016)[51]Starr等(1998)[53]Varga等(2006)[12] c.1621G>A p.G541S 轻度/中度听力损失 极重度听力损失 Kaga等(2016)[3]Matsunaga等(2012)[54]Zhang等(2016)[30] c.1841G>A p.G614E 轻度听力损失 重度听力损失 Romanos等(2009)[55] c.2382_2383delC p.L795Sfs*5 中度听力损失 / Zhang等(2016)[30] c.2521G>A p.E841K 低频中度听力损失 全频中度听力损失 Forli等(2023)[52] c.2975_2978delAG p.Q994Vfs*7 轻度/中度听力损失 中度/重度听力损失 Wang等(2010)[28]Zhang等(2016)[30] c.3239G>C p.R1080P 轻度听力损失 重度听力损失 Romanos等(2009)[55] c.3346C>T p.R1116X 轻度听力损失 轻度/极重度听力损失 Strenzke等(2016)[51]Starr等(1998)[53]Varga等(2006)[12] c.4189C>T p.R1607W 轻度/中度听力损失 中度/重度听力损失 Wang等(2010)[28]Zhang等(2016)[30] c.4882C>A p.P1628T 正常 轻度听力损失 Zhu等(2021)[23] c.5098G>C p.E1700Q 正常 轻度听力损失 Zhu等(2021)[23] c.5410_5412delGAG p.E1804del 正常/轻度听力损失 重度/极重度听力损失 Marlin等(2010)[56] c.(897+1_898-1)_(1579+1_1580-1) del - 低频中度听力损失 全频中度听力损失 Forli等(2023)[52] 
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