Genomic profiling supports the diagnosis of primary ciliary dyskinesia and reveals novel candidate genes and genetic variants.
Genomic profiling supports the diagnosis of primary ciliary dyskinesia and reveals novel candidate genes and genetic variants.
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DOI：
10.1371/journal.pone.0205422
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Pavlovic S
中科院分区：
文献类型：
--
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
原发性纤毛运动障碍（PCD）是一种罕见的常染色体隐性遗传或X连锁疾病，主要影响肺部。呼吸道纤毛功能障碍会引起慢性鼻窦炎、咳嗽、鼻炎、传导性听力损失和复发性肺部感染伴支气管扩张等症状。现在众所周知，致病性遗传变化导致纤毛功能障碍。在这里，我们报告使用临床外显子组为基础的NGS方法，以揭示潜在的遗传原因，在队列中的21例患者诊断的PCD。通过检测18种（12种新的）潜在致病性遗传变异，我们确定了11例（9例无关）患者的遗传原因。在6个PCD致病基因以及SPAG 16和SPAG 17基因中检测到遗传变异，这些基因在PCD患者中迄今未检测到，但与PCD的一些症状有关。在我们的队列中最常见的突变基因是DNAH 5（27.77%）。所鉴定的变异体为纯合、复合杂合和反式杂合。对于DNAI 1基因中一种新的纯合遗传变异的详细表征（c. 947_948insG，p.Thr318TyrfsTer11），进行RT-qPCR和蛋白质印迹分析。本研究应用分子诊断方法分析了29个PCD致病基因和相关基因。突变检出率为50%，发现了12个新的突变，并指出了两个可能的新的PCD候选基因。
Primary ciliary dyskinesia (PCD) is a rare inherited autosomal recessive or X-linked disorder that mainly affects lungs. Dysfunction of respiratory cilia causes symptoms such as chronic rhinosinusitis, coughing, rhinitis, conductive hearing loss and recurrent lung infections with bronchiectasis. It is now well known that pathogenic genetic changes lead to ciliary dysfunction. Here we report usage of clinical-exome based NGS approach in order to reveal underlying genetic causes in cohort of 21 patient with diagnosis of PCD. By detecting 18 (12 novel) potentially pathogenic genetic variants, we established the genetic cause of 11 (9 unrelated) patients. Genetic variants were detected in six PCD disease-causing genes, as well as in SPAG16 and SPAG17 genes, that were not detected in PCD patients so far, but were related to some symptoms of PCD. The most frequently mutated gene in our cohort was DNAH5 (27.77%). Identified variants were in homozygous, compound heterozygous and trans-heterozygous state. For detailed characterization of one novel homozygous genetic variant in DNAI1 gene (c. 947_948insG, p. Thr318TyrfsTer11), RT-qPCR and Western Blot analysis were performed. Molecular diagnostic approach applied in this study enables analysis of 29 PCD disease-causing and related genes. It resulted in mutation detection rate of 50% and enabled discovery of twelve novel mutations and pointed two possible novel PCD candidate genes.
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影响因子：
4.1
作者：
Boaretto, Francesca;Snijders, Deborah;Vazza, Giovanni
通讯作者：
Vazza, Giovanni
影响因子：
11.4
作者：
Howard, MT;Aggarwal, G;Atkins, JF
通讯作者：
Atkins, JF
DOI：
10.1164/rccm.200303-365oc
发表时间：
2004-02-15
影响因子：
24.7
作者：
Noone, PG;Leigh, MW;Knowles, MR
通讯作者：
Knowles, MR
影响因子：
10
作者：
Frija-Masson, Justine;Bassinet, Laurence;Maitre, Bernard
通讯作者：
Maitre, Bernard
影响因子：
3.9
作者：
Antony, Dinu;Becker-Heck, Anita;Zariwala, Maimoona A.;Schmidts, Miriam;Onoufriadis, Alexandros;Forouhan, Mitra;Wilson, Robert;Taylor-Cox, Theresa;Dewar, Ann;Jackson, Claire;Goggin, Patricia;Loges, Niki T.;Olbrich, Heike;Jaspers, Martine;Jorissen, Mark;Leigh, Margaret W.;Wolf, Whitney E.;Daniels, M. Leigh Anne;Noone, Peadar G.;Ferkol, Thomas W.;Sagel, Scott D.;Rosenfeld, Margaret;Rutman, Andrew;Dixit, Abhijit;O'Callaghan, Christopher;Lucas, Jane S.;Hogg, Claire;Scambler, Peter J.;Emes, Richard D.;Chung, Eddie M. K.;Shoemark, Amelia;Knowles, Michael R.;Omran, Heymut;Mitchison, Hannah M.
通讯作者：
Mitchison, Hannah M.