Clinical studies of families with hearing loss attributable to mutations in the connexin 26 gene (GJB2/DFNB1)
Clinical studies of families with hearing loss attributable to mutations in the connexin 26 gene (GJB2/DFNB1)
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DOI：
10.1542/peds.103.3.546
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发表时间：
1999-03-01
期刊：
影响因子：
8
通讯作者：
Kimberling, WJ
中科院分区：
文献类型：
--
作者：
Cohn, ES;Kelley, PM;Kimberling, WJ
客观的。这项回顾性研究描述了与遗传性听力损失的最常见原因相关的表型。儿童耳聋的发生率估计为 1/500。一半的听力损失是遗传性的，类似于 80% 的遗传性听力损失是非综合征性的，以常染色体隐性方式遗传。大约 50% 的儿童非综合征性隐性听力损失是由连接蛋白 26 (Cx26) 基因 (GJB2/DFNB1) 突变引起的，使其成为常染色体隐性遗传性非综合征性听力损失的最常见形式，携带率估计高达 2.8%。一种突变 35delG 占该基因突变的 75% 至 80%。方法。对来自 24 个家庭的 46 名个人进行了听力损失检查，这些人是 Cx26 突变纯合子或复合杂合子。对这些个体的一部分进行了前庭功能、耳声发射、听性脑干反应、颞骨计算机断层扫描、心电图、尿液分析、畸形和甲状腺功能的检查。结果。尽管所有人都有听力障碍，但没有观察到一致的听力表型。听力损失从轻度到中度到重度不等，甚至在常见突变 35delG 纯合的家族中也是如此，这表明其他因素改变了 Cx26 突变的表型效应。此外，在许多病例中观察到听力损失呈进行性。未发现与内耳异常、甲状腺功能障碍、心脏传导缺陷、尿液分析、畸形特征或视网膜异常之间的关联。结论。确诊听力损失的新生儿应进行 Cx26 测试。 Cx26 测试将有助于定义一个群体，其中大约 60% 的人患有严重或严重的听力损失，需要积极的语言干预（其中许多患者将是人工耳蜗的候选者）。
Objective. This retrospective study describes the phenotype associated with the single most common cause of genetic hearing loss. The frequency of childhood deafness is estimated at 1/500. Half of this hearing loss is genetic and similar to 80% of genetic hearing loss is nonsyndromic and inherited in an autosomal recessive manner. Approximately 50% of childhood nonsyndromic recessive hearing loss is caused by mutations in the connexin 26 (Cx26) gene (GJB2/DFNB1), making it the most common form of autosomal recessive nonsyndromic hearing loss with a carrier rate estimated to be as high as 2.8%. One mutation, 35delG, accounts for similar to 75% to 80% of mutations at this gene.Methods. Hearing loss was examined in 46 individuals from 24 families who were either homozygous or compound heterozygous for Cx26 mutations. A subset of these individuals were examined for vestibular function, otoacoustic emissions, auditory brainstem response, temporal bone computed tomography, electrocardiography, urinalyses, dysmorphology, and thyroid function.Results. Although all persons had hearing impairment, no consistent audiologic phenotype was observed. Hearing loss varied from mild-moderate to profound, even within the group of families homozygous for the common mutation 35delG, suggesting that other factors modify the phenotypic effects of mutations in Cx26. Furthermore, the hearing loss was observed to be progressive in a number of cases. No associations with inner ear abnormality, thyroid dysfunction, heart conduction defect, urinalyses, dysmorphic features, or retinal abnormality were noted.Conclusion. Newborns with confirmed hearing loss should have Cx26 testing. Cx26 testing will help define a group in which similar to 60% will have profound or severe-profound hearing loss and require aggressive language intervention (many of these patients will be candidates for cochlear implants).