Hilgert Nele, Smith Richard J H, Van Camp Guy
Department of Medical Genetics, University of Antwerp (UA), Universiteitsplein 1, B-2610 Antwerp, Belgium.
Department of Otolaryngology-Head and Neck Surgery, University of Iowa, Iowa city, IA 52242, USA.
Mutat Res. 2009 Mar-Jun;681(2-3):189-196. doi: 10.1016/j.mrrev.2008.08.002. Epub 2008 Aug 29.
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, although 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 recognisable feature (i.e. SLC26A4 and enlarged vestibular aqueduct); or (3) a recognisable 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.
听力障碍是最常见的感觉障碍，每500名新生儿中就有1人患病。由于有46个基因与非综合征性听力损失有关，所以它也是一种极其异质性的特征。在这里，我们首次对全球范围内，更具体地说是在高加索人群中，非综合征性耳聋基因中报告的所有突变进行了分类。与常染色体隐性非综合征性听力损失相关的最常见基因是GJB2，它导致了一半以上的病例，其次是SLC26A4、MYO15A、OTOF、CDH23和TMC1。虽然WFS1、KCNQ4、COCH和GJB2中报告的突变频率略高，但与常染色体显性非综合征性听力损失相关的基因都没有在病例中占主导地位。目前只有少数这些基因被纳入基因诊断，选择标准通常反映：（1）作为耳聋原因的高频率（即GJB2）；（2）与另一种可识别特征的关联（即SLC26A4和扩大的前庭导水管）；或（3）一种可识别的听力图（即WFS1）。在过去几年中已经开发出了新的强大的DNA测序技术，但尚未应用于DNA诊断。在未来5年内可能会采用这些技术，这将在检测能力和成本效益方面带来突破。与目前分析一个或几个基因不同，将有可能分析大多数（如果不是全部）耳聋基因。这种能力将极大地改善DNA诊断，提供基于基因的突变频率的流行病学数据，并揭示新的基因型-表型相关性。
