Jung Joonho, Jang Seung Hyun, Won Dongju, Gee Heon Yung, Choi Jae Young, Jung Jinsei
Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
Department of Pharmacology, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
J Clin Med. 2024 Aug 16;13(16):4851. doi: 10.3390/jcm13164851.
Mutations in Wolfram syndrome 1 () cause Wolfram syndrome and autosomal dominant non-syndromic hearing loss DFNA6/14/38. To date, more than 300 pathogenic variants of have been identified. Generally, the audiological phenotype of Wolfram syndrome or DFNA6/14/38 is characterized by low-frequency hearing loss; however, this phenotype is largely variable. Hence, there is a need to better understand the diversity in audiological and vestibular profiles associated with WFS1 variants, as this can have significant implications for diagnosis and management. This study aims to investigate the clinical characteristics, audiological phenotypes, and vestibular function in patients with DFNA6/14/38. Whole-exome or targeted deafness gene panel sequencing was performed to confirm the pathogenic variants in patients with genetic hearing loss. We identified nine independent families with affected individuals who carried a heterozygous pathogenic variant of . The onset of hearing loss varied from the first to the fifth decade. On a pure-tone audiogram, hearing loss was symmetrical, and the severity ranged from mild to severe. Notably, either both low-frequency and high-frequency or all-frequency-specific hearing loss was observed. However, hearing loss was non-progressive in all types. In addition, vestibular impairment was identified in patients with DFNA6/14/38, indicating that impaired may also affect the vestibular organs. Diverse audiological and vestibular profiles were observed in patients with pathogenic variants of These findings highlight the importance of comprehensive audiological and vestibular assessments in patients with mutations for accurate diagnosis and management.
Wolfram 综合征 1 基因（WFS1）突变可导致 Wolfram 综合征以及常染色体显性非综合征性听力损失 DFNA6/14/38。迄今为止，已鉴定出 300 多个 WFS1 的致病变体。一般来说，Wolfram 综合征或 DFNA6/14/38 的听力学表型以低频听力损失为特征；然而，这种表型差异很大。因此，有必要更好地了解与 WFS1 变体相关的听力学和前庭特征的多样性，因为这对诊断和管理具有重要意义。本研究旨在调查 DFNA6/14/38 患者的临床特征、听力学表型和前庭功能。对遗传性听力损失患者进行全外显子组或靶向耳聋基因panel测序以确认致病变体。我们确定了九个独立的家系，其中受影响的个体携带 WFS1 的杂合致病变体。听力损失的发病年龄从第一个十年到第五个十年不等。在纯音听力图上，听力损失是对称的，严重程度从轻度到重度不等。值得注意的是，观察到低频和高频或全频特异性听力损失。然而，所有类型的听力损失均无进展。此外，在 DFNA6/14/38 患者中发现了前庭功能障碍，这表明 WFS1 功能受损可能也会影响前庭器官。在携带 WFS1 致病变体的患者中观察到了不同的听力学和前庭特征。这些发现强调了对 WFS1 突变患者进行全面听力学和前庭评估对于准确诊断和管理的重要性。
