Evaluation of a Deafness GeneChip

描述（由申请人提供）：听力损失是最常见的感觉障碍，患病率为1 / 250新生儿（NCHAM, 2004）。这些儿童中有一半以上的听力障碍与遗传有关，涉及93个非综合征基因座（Van Camp & Smith, 2004）和500多个综合征基因座（OMIM, 2004）。尽管发现了41种非综合征性听力损失的基因，但很少有基因测试被开发出来，这主要是因为为这些基因提供完整的测序测试的成本巨大，而这些基因几乎没有已知的常见突变。为了解决这个问题，一种耳聋基因芯片已经被创造出来，它包含了8个已知与隐性非综合征性听力损失有关的基因：GJB2、MYO6、MYO7A、OTOF、PRES、TMIE、TMPRSS3和USH1C。虽然这项技术看起来很有希望作为一种经济有效的方法来扩大听力损失的基因检测，但它对临床诊断来说是新的，需要严格的验证。该项目将确定156例原因不明的语前非综合征感音神经性听力损失（SNHL）患者，并比较基因芯片技术和传统测序产生的基因序列。这将用于确定基本呼叫率，假阳性率和假阴性率，这将反过来用于计算聋基因芯片的分析灵敏度和效率和有效性，与传统的双脱氧DNA测序这些基因相比。此外，来自这156名患者序列的数据将用于识别突变，从而确定耳聋基因芯片的临床敏感性，以及这些基因对语前非综合征性SNHL的相对贡献。

DESCRIPTION (provided by applicant): Hearing loss is the most common sensory impairment with a prevalence of 1 in 250 births (NCHAM, 2004). Over half of these children have a genetic cause for their hearing impairment with 93 nonsyndromic loci (Van Camp & Smith, 2004) and over 500 syndromic loci (OMIM, 2004) implicated. Despite the discovery of 41 of the genes for nonsyndromic hearing loss, very few genetic tests have been developed, largely due to the enormous cost of offering full sequencing tests for these genes with few known common mutations. To address this problem, a Deafness GeneChip has been created which contains 8 genes known to be involved in recessive nonsyndromic hearing loss: GJB2, MYO6, MYO7A, OTOF, PRES, TMIE, TMPRSS3, and USH1C. Although this technology looks promising as a cost-effective way to expand genetic testing for hearing loss, it is new to clinical diagnostics and needs to be validated in a rigorous manner. This project will identify 156 patients with an unknown cause of prelingual nonsyndromic sensorineural hearing loss (SNHL) and compare their gene sequences generated by both GeneChip technology and traditional sequencing. This will be used to determine the base call rate, false positive rate, and false negative rate which will in turn be used to calculate the analytical sensitivity and the efficiency and effectiveness of the Deafness GeneChip, as compared to traditional dideoxy DNA sequencing of these genes. In addition, the data from the sequences of these 156 patients will be used to identify mutations and thereby determine the clinical sensitivity of this Deafness GeneChip and the relative contribution of each of these genes to prelingual nonsyndromic SNHL.