Department of Otolaryngology, University of Miami, Miami, Florida 33136, USA.
Laryngoscope. 2011 Apr;121(4):811-4. doi: 10.1002/lary.21422. Epub 2011 Feb 1.
The aim of the study is to assess clinical characteristics of individuals with nonsyndromic sensorineural hearing loss (NSSNHL) with genetic mutations in GJB2 and/or GJB6. We describe and compare one group with biallelic mutations against a group of heterozygote mutation carriers.
A total of 350 patients between the ages of 3 months and 80 years referred to a tertiary care outpatient otology practice for NSSNHL were screened for genetic mutations. Direct sequencing of GJB2 and polymerase chain reaction analysis of GJB6 was performed and clinical data from history and physical, audiologic testing and radiographic studies were reviewed.
Thirty-two patients were found to have biallelic mutations (incidence of 9.1%). Twenty-five patients were found to have only one GJB2 mutation (incidence of 7.1%). Severe to profound hearing loss occurred in 85% of the homozygote group and 38% of the heterozygote group. Both groups similarly had a propensity toward bilateral, symmetric, nonprogressive hearing loss with rare inner ear malformations on radiologic imaging.
These two patient populations have similar incidences in a cohort of patients evaluated for NSSNHL, which is higher than general population heterozygote carrier rates. Heterozygote mutation carriers had less hearing impairment, but most other factors demonstrated no differences. These results support the theory of an unidentified genetic factor contributing to hearing loss in some heterozygote carriers. Therefore, genetic counseling should consider the complexity of their genetic factors and the limitations of current screening.
本研究旨在评估 GJB2 和/或 GJB6 基因突变的非综合征型感音神经性听力损失（NSSNHL）个体的临床特征。我们描述并比较了两组纯合突变与杂合突变携带者。
共对 350 名年龄在 3 个月至 80 岁之间的 NSSNHL 患者进行了基因筛查。对 GJB2 进行直接测序，对 GJB6 进行聚合酶链反应分析，并回顾病史和体格检查、听力学测试和影像学研究的临床数据。
发现 32 例患者存在纯合突变（发生率为 9.1%）。仅发现 25 例患者存在一个 GJB2 突变（发生率为 7.1%）。纯合子组 85%和杂合子组 38%的患者均出现严重至重度听力损失。两组患者均存在双侧、对称、非进行性听力损失的倾向，且影像学检查罕见内耳畸形。
在评估 NSSNHL 的患者队列中，这两个患者群体的发生率均高于一般人群的杂合突变携带者率。杂合突变携带者的听力损失程度较轻，但大多数其他因素没有差异。这些结果支持了一个未被识别的遗传因素导致某些杂合突变携带者听力损失的理论。因此，遗传咨询应考虑到其遗传因素的复杂性以及当前筛查的局限性。
