Forty-six genes causing nonsyndromic hearing impairment: which ones should be analyzed in DNA diagnostics?
Forty-six genes causing nonsyndromic hearing impairment: which ones should be analyzed in DNA diagnostics?
复制标题
DOI：
10.1016/j.mrrev.2008.08.002
复制
发表时间：
2009-03
影响因子：
5.3
通讯作者：
Van Camp, Guy
中科院分区：
文献类型：
--
作者：
Hilgert, Nele;Smith, Richard J. H.;Van Camp, Guy
听力障碍是最常见的感觉障碍，每500个新生儿中就有1个。有46个基因与非综合征性听力损失有关，这也是一个极其异质的特征。在这里，我们第一次对所有非综合征性耳聋基因的突变进行了分类，包括世界范围内的，更具体地说是在高加索人中。与常染色体隐性遗传性非综合征性听力损失有关的最常见基因是GJB 2，占一半以上，其次是SLC 26 A4，MYO 15 A，OTOF，CDH 23和TMC 1。与常染色体显性遗传非综合征性听力损失相关的基因中没有一个占病例的优势。突变在WFS 1、KCNQ 4、COCH和GJB 2中报告的频率更高。这些基因中只有少数目前被包括在遗传诊断中，选择标准通常反映：1）作为耳聋原因的高频率（即GJB 2）; 2）与另一个可识别的特征（即SLC 26 A4和前庭水管扩大）相关;或3）可识别的音频特征（即WFS 1）。在过去的几年中，已经开发了新的和强大的DNA测序技术，但尚未找到进入DNA诊断的方法。这些技术很可能在未来5年内实现，并将在电力和成本效率方面带来突破。与目前的一个或几个基因相比，分析大多数（如果不是全部）耳聋基因将成为可能。这种能力将极大地改善DNA诊断，提供基于基因突变频率的流行病学数据，并揭示新的基因型-表型相关性。
Hearing impairment is the most common sensory disorder, present in 1 of every 500 newborns. With 46 genes implicated in nonsyndromic hearing loss, it is also an extremely heterogeneous trait. Here, we categorize for the first time all mutations reported in nonsyndromic deafness genes, both worldwide and more specifically in Caucasians. The most frequent genes implicated in autosomal recessive nonsyndromic hearing loss are GJB2, which is responsible for more than half of cases, followed by SLC26A4, MYO15A, OTOF, CDH23 and TMC1. None of the genes associated with autosomal dominant nonsyndromic hearing loss accounts for a preponderance of cases. Mutations are somewhat more frequently reported in WFS1, KCNQ4, COCH and GJB2. Only a minority of these genes is currently included in genetic diagnostics, the selection criteria typically reflecting: 1) high frequency as a cause of deafness (i.e. GJB2); 2) association with another recognizable feature (i.e. SLC26A4 and enlarged vestibular aqueduct); or 3) a recognizable audioprofile (i.e. WFS1). New and powerful DNA sequencing technologies have been developed over the past few years, but have not yet found their way into DNA diagnostics. Implementing these technologies is likely to happen within the next 5 years, and will cause a breakthrough in terms of power and cost efficiency. It will become possible to analyze most - if not all - deafness genes, as opposed to one or a few genes currently. This ability will greatly improve DNA diagnostics, provide epidemiological data on gene-based mutation frequencies, and reveal novel genotype-phenotype correlations.
登录
查看更多内容
影响因子：
4
作者：
del Castillo, FJ;Rodríguez-Ballesteros, M;del Castillo, I
通讯作者：
del Castillo, I
影响因子：
4
作者：
de Zwart-Storm, E. A.;Hamm, H.;van Steensel, M. A. M.
通讯作者：
van Steensel, M. A. M.
影响因子：
158.5
作者：
del Castillo, I;Villamar, M;Moreno, F
通讯作者：
Moreno, F
DOI：
10.1016/j.ijporl.2007.09.023
发表时间：
2008-02-01
影响因子：
1.5
作者：
Alasti, Fatemeh;Sanati, Mohammad Hossein;Van Camp, Guy
通讯作者：
Van Camp, Guy
影响因子：
2.1
作者：
Kemperman, MH;De Leenheer, EMR;Cremers, CWRJ
通讯作者：
Cremers, CWRJ