Primárna ciliárna dyskinéza (PCD) je zriedkavé, geneticky heterogénne ochorenie, ktoré patrí do širokej skupiny ciliopatií. Je charakterizované abnormálnou ultraštruktúrou a funkciou pohyblivých riasiniek s následným narušením mukociliárneho transportu respiračného epitelu. Klinická manifestácia ochorenia je u takmer polovice pacientov nešpecifická a často sa prekrýva s najčastejšími respiračnými ochoreniami. Preto stanovenie jednoznačnej diagnózy je veľmi náročné a vyžaduje komplexný multidisciplinárny prístup v špecializovanom centre s kombináciou viacerých diagnostických metód. Vzhľadom na genetický pôvod ochorenia, v diagnostickom procese zohráva analýza DNA významnú úlohu. V súčasnosti sa do popredia dostáva metóda sekvenovania novej generácie (NGS-next generation sequencing), ktorá umožňuje vyšetriť veľké množstvo génov v jednej reakcii, čím urýchli genetickú analýzu. Cieľom prehľadového článku je zhrnúť aktuálne poznatky a poukázať na nové možnosti diagnostiky primárnej ciliárnej dyskinézy pomocou sekvenovania novej generácie.
Primary ciliary dyskinesia (PCD) is a rare, genetically heterogeneous disease that belongs to a large group of ciliopathies. It is characterized by abnormal ultrastructure and function of motile cilia with subsequent disturbanceof the mucociliary transport of the respiratory epithelium. Clinical manifestation of the disease is nonspecific inalmost half the patients and often overlaps with the most common respiratory diseases. Therefore, establishinga clear diagnosis is very demanding and requires a comprehensive multidisciplinary approach combining multiplediagnostic methods in a specialized center. Due to the genetic origin of the disease, DNA analysis plays an important role in the diagnostic process. At present, next generation sequencing (NGS) becomes an increasingly useful method as it allows examination of large numbers of genes in a single reaction, thus accelerating the genetic analysis.The review article aimed to summarize current knowledge of this topic and show new possibilities for diagnosing PCD using NGS.
Autosomal-dominant polycystic kidney disease (ADPKD) is an inherited disease that results in multiple kidney cysts, and it is a common cause of end-stage renal disease. Recent studies have shown that disease progression can be slowed by simultaneous disruption of the primary cilium and polycystins. The exact genetic mechanism of this process is still unknown. The aim of the present study was to characterize the mutation profile of ciliary signalling pathways in the renal epithelial cells of ADPKD patients. In our study, we performed an analysis of 110 genes encoding the components of Sonic Hedgehog, Hippo, Notch, Wnt and planar cell polarity signalling (PCP) by targeted next-generation sequencing. We analysed 10 formalin-fixed, paraffinembedded (FFPE) tissue samples of patients with ADPKD. We identified a unique mutation profile in each of the analysed ADPKD samples, which was characterized by the presence of pathogenic variants in eight to 11 genes involved in different signalling pathways. Despite the significant genetic heterogeneity of ADPKD, we detected five genes whose genetic variants affected most ADPKD samples. The pathogenic variants in NCOR2 and LRP2 genes were present in all analysed samples of ADPKD. In addition, eight out of 10 samples showed a pathogenic variant in the MAML2 and FAT4 genes, and six out of 10 samples in the CELSR1 gene. In our study, we identified the signalling molecules that may contribute to the cystogenesis and may represent potential targets for the development of new ADPKD treatments.
- MeSH
- DNA vazebné proteiny genetika MeSH
- dospělí MeSH
- jaderné proteiny genetika MeSH
- kadheriny genetika MeSH
- kationtové kanály TRPP genetika MeSH
- korepresor 2 jaderného receptoru genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- mutace genetika MeSH
- nádorové supresorové proteiny genetika MeSH
- pilotní projekty MeSH
- polarita buněk genetika fyziologie MeSH
- polycystická choroba ledvin genetika metabolismus patologie MeSH
- polycystické ledviny autozomálně dominantní genetika metabolismus patologie MeSH
- progrese nemoci MeSH
- protein 2 související s LDL-receptory genetika MeSH
- signální transdukce genetika fyziologie MeSH
- transkripční faktory genetika MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
