Identification and Classification of Novel Genetic Variants: En Route to the Diagnosis of Primary Ciliary Dyskinesia.
Identification and Classification of Novel Genetic Variants: En Route to the Diagnosis of Primary Ciliary Dyskinesia.
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DOI：
10.3390/ijms22168821
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发表时间：
2021-08-17
影响因子：
5.6
通讯作者：
Andjelkovic M
中科院分区：
文献类型：
--
作者：
Stevanovic N;Skakic A;Minic P;Sovtic A;Stojiljkovic M;Pavlovic S;Andjelkovic M
原发性纤毛运动障碍（PCD）是由纤毛运动功能受损引起的疾病。PCD主要影响肺部和生殖器官。遗传是常染色体隐性遗传和X连锁。PCD患者具有不同的临床表现，因此使得建立适当的诊断具有挑战性。下一代测序（NGS）技术用于诊断目的的实用程序允许更好地了解PCD遗传背景。然而，识别特定的致病变异是困难的。本研究的主要目的是创建一个独特的指南，使PCD相关基因内的新型遗传变异的评估标准化。设计的流水线由三个主要步骤组成：（1）基因/变体的测序、检测和鉴定;（2）根据其效应对变体进行分类;以及（3）使用计算机结构和功能分析进行变体表征。通过分析在已知的PCD致病基因（DNAI 1）和新的候选基因（SPAG 16）中检测到的变体，验证了该管道。该管道的应用导致了潜在致病变体的鉴定，以及变体致病性的验证，通过它们在转录、翻译和翻译后水平上的分析。该管道的应用导致PCD诊断的确认，并使得能够从候选基因转变为PCD致病基因。
Primary ciliary dyskinesia (PCD) is a disease caused by impaired function of motile cilia. PCD mainly affects the lungs and reproductive organs. Inheritance is autosomal recessive and X-linked. PCD patients have diverse clinical manifestations, thus making the establishment of proper diagnosis challenging. The utility of next-generation sequencing (NGS) technology for diagnostic purposes allows for better understanding of the PCD genetic background. However, identification of specific disease-causing variants is difficult. The main aim of this study was to create a unique guideline that will enable the standardization of the assessment of novel genetic variants within PCD-associated genes. The designed pipeline consists of three main steps: (1) sequencing, detection, and identification of genes/variants; (2) classification of variants according to their effect; and (3) variant characterization using in silico structural and functional analysis. The pipeline was validated through the analysis of the variants detected in a well-known PCD disease-causing gene (DNAI1) and the novel candidate gene (SPAG16). The application of this pipeline resulted in identification of potential disease-causing variants, as well as validation of the variants pathogenicity, through their analysis on transcriptional, translational, and posttranslational levels. The application of this pipeline leads to the confirmation of PCD diagnosis and enables a shift from candidate to PCD disease-causing gene.
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影响因子：
13.6
作者：
Dai C;Gu W
通讯作者：
Gu W
影响因子：
14.8
作者：
Kelley LA;Mezulis S;Yates CM;Wass MN;Sternberg MJ
通讯作者：
Sternberg MJ
影响因子：
3.7
作者：
Andjelkovic M;Minic P;Vreca M;Stojiljkovic M;Skakic A;Sovtic A;Rodic M;Skodric-Trifunovic V;Maric N;Visekruna J;Spasovski V;Pavlovic S
通讯作者：
Pavlovic S
DOI：
10.1073/pnas.1715915115
发表时间：
2018-02-06
影响因子：
11.1
作者：
Horani, Amjad;Ustione, Alessandro;Brody, Steven L.
通讯作者：
Brody, Steven L.
影响因子：
10
作者：
Frija-Masson, Justine;Bassinet, Laurence;Maitre, Bernard
通讯作者：
Maitre, Bernard