Development of a molecular diagnostic test for Retinitis Pigmentosa in the Japanese population
Development of a molecular diagnostic test for Retinitis Pigmentosa in the Japanese population
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DOI：
10.1007/s10384-018-0601-x
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发表时间：
2018-07-01
影响因子：
2.4
通讯作者：
Takahashi, Masayo
中科院分区：
文献类型：
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作者：
Maeda, Akiko;Yoshida, Akiko;Takahashi, Masayo
视网膜色素变性是遗传性视网膜营养不良中最常见的一种，由不同的遗传变异引起。到目前为止，已经发现了60多个致病基因。建立高灵敏度、高特异度、高性价比的分子诊断试验对患者和临床医生都是有益的。在这里，我们开发了一种日本人群中RP的临床诊断测试。对诊断技术、前瞻性、临床和实验研究进行了评估。建立了一个由39个基因组成的小组，该小组报告了在日本患者中导致RP的基因。应用下一代序列(NGS)技术对94例RP及RP相关疾病先证者进行分析。在解释了检测到的遗传变异后，一个包括临床医生、研究人员和遗传顾问在内的多学科团队基于对遗传变异和临床表型的研究进行了分子诊断。NGS分析从94个先证者中发现了14,343个变异。其中，83个先证者的189个变异体(占全部病例的88.3%)被选为致病变异体，先证者(68.1%)有致病变异体。对这些病例进行分析后，有43个先证者(45.7%)作出了分子诊断。目前的系统结合补充Sanger测序的最终分子诊断率为47.9%(94例中45例)。RP面板在检测遗传变异方面具有显著优势，分子诊断率高。这种类型的种族特异性高通量基因分型使我们能够进行具有成本效益和临床实用的基因诊断测试。
Retinitis Pigmentosa (RP) is the most common form of inherited retinal dystrophy caused by different genetic variants. More than 60 causative genes have been identified to date. The establishment of cost-effective molecular diagnostic tests with high sensitivity and specificity can be beneficial for patients and clinicians. Here, we developed a clinical diagnostic test for RP in the Japanese population.Evaluation of diagnostic technology, Prospective, Clinical and experimental study.A panel of 39 genes reported to cause RP in Japanese patients was established. Next generation sequence (NGS) technology was applied for the analyses of 94 probands with RP and RP-related diseases. After interpretation of detected genetic variants, molecular diagnosis based on a study of the genetic variants and a clinical phenotype was made by a multidisciplinary team including clinicians, researchers and genetic counselors.NGS analyses found 14,343 variants from 94 probands. Among them, 189 variants in 83 probands (88.3% of all cases) were selected as pathogenic variants and 64 probands (68.1%) have variants which can cause diseases. After the deliberation of these 64 cases, molecular diagnosis was made in 43 probands (45.7%). The final molecular diagnostic rate with the current system combining supplemental Sanger sequencing was 47.9% (45 of 94 cases).The RP panel provides the significant advantage of detecting genetic variants with a high molecular diagnostic rate. This type of race-specific high-throughput genotyping allows us to conduct a cost-effective and clinically useful genetic diagnostic test.