Isik Esra, Onay Huseyin, Atik Tahir, Canda Ebru, Cogulu Ozgur, Coker Mahmut, Ozkinay Ferda
Subdivision of Pediatric Genetics, Department of Pediatrics, Ege University, Izmir, Turkey.
Department of Medical Genetics, Ege University, Izmir, Turkey.
Eur J Med Genet. 2019 Oct;62(10):103725. doi: 10.1016/j.ejmg.2019.103725. Epub 2019 Jul 15.
Next generation sequencing has provided great advancements in genetic diagnosis of Mendalian disorders. Simultaneous sequencing of many genes has become increasingly cheaper and faster. Recently, a number of gene panels have been established for the diagnosis of specific disease groups. The aim of this study is to evaluate the utility of an inherited disease panel in pediatric onset Mendelian diseases. Two hundred and seventeen probands and 10 carriers molecularly analyzed using a TruSight Inherited Disease Panel which included 552 genes responsible for pediatric onset Mendelian disorders, were enrolled in the study. The clinical phenotype, sequencing data, pretest and posttest diagnoses were evaluated. The patients in the study were classified into two groups. Group 1 (n:209) included the patients having a clinical diagnosis prior to molecular analysis. Group 2 (n:18) included the patients undiagnosed clinically prior to molecular analysis. Targeted panel provided a molecular diagnosis in 37% (84 of 227 cases) of all cases. The molecular diagnostic rate was 40.2% in patients with a specific prior clinical diagnosis. However, in patients having no primary clinical diagnosis no pathogenic variants were found. In 14 patients, a molecular diagnosis differing from the established clinical diagnosis was made. In conclusion, a targeted panel covering a high number of genes responsible for broad phenotypic spectrum can provide improved levels of diagnosis in patients with pediatric onset Mendelian diseases. A careful clinical evaluation of patients prior to the application of a next generation sequencing method leads to the best alternative approach for a conclusive molecular diagnosis.
下一代测序技术在孟德尔疾病的基因诊断方面取得了巨大进展。同时对多个基因进行测序变得越来越便宜且速度更快。最近，已经建立了一些用于诊断特定疾病组的基因检测板。本研究的目的是评估遗传性疾病检测板在儿童期发病的孟德尔疾病中的效用。使用包含552个负责儿童期发病孟德尔疾病的基因的TruSight遗传性疾病检测板对217名先证者和10名携带者进行分子分析，这些患者被纳入研究。对临床表型、测序数据、检测前和检测后的诊断进行了评估。研究中的患者分为两组。第1组（n = 209）包括在分子分析之前已有临床诊断的患者。第2组（n = 18）包括在分子分析之前临床未确诊的患者。靶向检测板在所有病例的37%（227例中的84例）中提供了分子诊断。在有特定先前临床诊断的患者中，分子诊断率为40.2%。然而，在没有初步临床诊断的患者中未发现致病变异。在14名患者中，做出了与既定临床诊断不同 的分子诊断。总之，一个涵盖大量负责广泛表型谱基因的靶向检测板可以提高儿童期发病孟德尔疾病患者的诊断水平。在应用下一代测序方法之前对患者进行仔细的临床评估会为得出确定性分子诊断带来最佳替代方法。
