Human Genetics Center, School of Public Health, The University of Texas Health Science Center, Houston, TX 77030, USA.
Clin Genet. 2013 Aug;84(2):132-41. doi: 10.1111/cge.12203. Epub 2013 Jun 19.
Retinitis pigmentosa (RP) is a heterogeneous set of inherited retinopathies with many disease-causing genes, many known mutations, and highly varied clinical consequences. Progress in finding treatments is dependent on determining the genes and mutations causing these diseases, which includes both gene discovery and mutation screening in affected individuals and families. Despite the complexity, substantial progress has been made in finding RP genes and mutations. Depending on the type of RP, and the technology used, it is possible to detect mutations in 30-80% of cases. One of the most powerful approaches to genetic testing is high-throughput 'deep sequencing', that is, next-generation sequencing (NGS). NGS has identified several novel RP genes but a substantial fraction of previously unsolved cases have mutations in genes that are known causes of retinal disease but not necessarily RP. Apparent discrepancy between the molecular defect and clinical findings may warrant reevaluation of patients and families. In this review, we summarize the current approaches to gene discovery and mutation detection for RP, and indicate pitfalls and unsolved problems. Similar considerations apply to other forms of inherited retinal disease.
色素性视网膜炎（RP）是一组具有多种遗传视网膜病变的异质性疾病，有许多致病基因、许多已知的突变，以及高度多样化的临床后果。寻找治疗方法的进展取决于确定导致这些疾病的基因和突变，这包括在受影响的个体和家庭中进行基因发现和突变筛查。尽管存在复杂性，但在寻找 RP 基因和突变方面已经取得了实质性进展。根据 RP 的类型和使用的技术，有可能在 30-80%的病例中检测到突变。基因检测最强大的方法之一是高通量“深度测序”，即下一代测序（NGS）。NGS 已经确定了几个新的 RP 基因，但以前未解决的病例中，相当一部分存在已知引起视网膜疾病但不一定是 RP 的基因的突变。分子缺陷与临床发现之间的明显差异可能需要重新评估患者和家庭。在这篇综述中，我们总结了当前用于 RP 的基因发现和突变检测的方法，并指出了陷阱和未解决的问题。其他形式的遗传性视网膜疾病也有类似的考虑因素。
