Department of Otolaryngology and Head and Neck Surgery. Marqués de Valdecilla University Hospital, Santander, Spain; Cell Cycle, Stem Cell Fate and Cancer Laboratory, Institute for Research Marqués de Valdecilla (IDIVAL), 39011 Santander, Spain; Faculty of Medicine. University of Cantabria, Santander, Spain.
Department of Radiology. Marqués de Valdecilla University Hospital, Santander, Spain.
Int J Pediatr Otorhinolaryngol. 2024 Nov;186:112082. doi: 10.1016/j.ijporl.2024.112082. Epub 2024 Aug 28.
Genetic variants in the OTOF gene are responsible for non-syndromic hearing loss with an autosomal recessive inheritance pattern. The objective of our work was to evaluate the clinical characteristics of patients with biallelic pathogenic variants in OTOF and their evolution after treatment.
A cohort of 124 patients with prelingual hearing loss, studied from 1996 to 2023, was included in this study. A genetic analysis was conducted to identify the type and frequency of variants in the OTOF gene and their relation to the clinical characteristics of the patients.
The homozygous p. Gln829* variant in the OTOF gene was detected in 3 probands (2.4 %) of a group of 124 individuals with prelingual hearing loss. Another 6 family members to a total of 9 individuals were finally included. All presented with severe/profound bilateral sensorineural hearing loss of congenital onset. Three of these individuals were diagnosed with auditory neuropathy spectrum disorder. One individual passed the OAE test during the screening program, and since he did not have risk factors for hearing loss that would warrant ABR testing, this led to a delay in his hearing loss diagnosis. Four individuals underwent cochlear implants (three bilateral) with good functional outcomes in three of them. However, in 17 familial cases with heterozygous variants, either no hearing loss was observed or it was within the expected range for their age.
Hearing loss secondary to the p.Gln829* variant of the OTOF gene is relatively rare in our medical area. Its presence in homozygosity is the cause of severe/profound bilateral prelingual sensorineural hearing loss, responsible for auditory neuropathy with a good response to cochlear implantation.
OTOF 基因中的遗传变异导致常染色体隐性遗传模式的非综合征性听力损失。我们的工作目的是评估 OTOF 基因中双等位致病性变异患者的临床特征及其治疗后的演变。
本研究纳入了 1996 年至 2023 年间研究的 124 例语前听力损失患者。进行基因分析以确定 OTOF 基因中变异的类型和频率及其与患者临床特征的关系。
在 124 名语前听力损失个体的一组中，发现了 3 名先证者（2.4%）携带 OTOF 基因的纯合 p.Gln829* 变异，另有 6 名家族成员共 9 人最终被纳入。所有患者均表现为先天性双侧重度/极重度感觉神经性听力损失。其中 3 例被诊断为听神经病谱系障碍。1 名个体在筛查计划中通过了 OAE 测试，由于他没有听力损失的风险因素需要进行 ABR 测试，这导致他的听力损失诊断延迟。4 名个体接受了人工耳蜗植入（3 例双侧），其中 3 名患者的功能结果良好。然而，在 17 例携带杂合变异的家族病例中，要么没有观察到听力损失，要么听力损失在其年龄预期范围内。
在我们的医疗领域，由 OTOF 基因的 p.Gln829* 变异引起的听力损失相对较少。其纯合性导致双侧重度/极重度语前感觉神经性听力损失，引起听觉神经病，对人工耳蜗植入有良好的反应。
