Genomic profiling supports the diagnosis of primary ciliary dyskinesia and reveals novel candidate genes and genetic variants
Аутори
Anđelković, MarinaMinić, Predrag
Vreca, Misa
Stojiljković, Maja
Skakić, Anita
Sovtić, Aleksandar
Rodić, Milan
Skodrić-Trifunović, Vesna
Marić, Nina
Visekruna, Jelena
Spasovski, Vesna
Pavlović, Sonja
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
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-heterozy...gous 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.
Извор:
PLoS One, 2018, 13, 10Издавач:
- Public Library Science, San Francisco
Финансирање / пројекти:
- Ретке болести: молекуларна патофизиологија, дијагностички и терапијски модалитети и социјални, етички и правни аспекти (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-41004)
DOI: 10.1371/journal.pone.0205422
ISSN: 1932-6203
PubMed: 30300419
WoS: 000446897200061
Scopus: 2-s2.0-85054724295
Институција/група
Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Anđelković, Marina AU - Minić, Predrag AU - Vreca, Misa AU - Stojiljković, Maja AU - Skakić, Anita AU - Sovtić, Aleksandar AU - Rodić, Milan AU - Skodrić-Trifunović, Vesna AU - Marić, Nina AU - Visekruna, Jelena AU - Spasovski, Vesna AU - Pavlović, Sonja PY - 2018 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/1146 AB - 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. PB - Public Library Science, San Francisco T2 - PLoS One T1 - Genomic profiling supports the diagnosis of primary ciliary dyskinesia and reveals novel candidate genes and genetic variants IS - 10 VL - 13 DO - 10.1371/journal.pone.0205422 ER -
@article{ author = "Anđelković, Marina and Minić, Predrag and Vreca, Misa and Stojiljković, Maja and Skakić, Anita and Sovtić, Aleksandar and Rodić, Milan and Skodrić-Trifunović, Vesna and Marić, Nina and Visekruna, Jelena and Spasovski, Vesna and Pavlović, Sonja", year = "2018", abstract = "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.", publisher = "Public Library Science, San Francisco", journal = "PLoS One", title = "Genomic profiling supports the diagnosis of primary ciliary dyskinesia and reveals novel candidate genes and genetic variants", number = "10", volume = "13", doi = "10.1371/journal.pone.0205422" }
Anđelković, M., Minić, P., Vreca, M., Stojiljković, M., Skakić, A., Sovtić, A., Rodić, M., Skodrić-Trifunović, V., Marić, N., Visekruna, J., Spasovski, V.,& Pavlović, S.. (2018). Genomic profiling supports the diagnosis of primary ciliary dyskinesia and reveals novel candidate genes and genetic variants. in PLoS One Public Library Science, San Francisco., 13(10). https://doi.org/10.1371/journal.pone.0205422
Anđelković M, Minić P, Vreca M, Stojiljković M, Skakić A, Sovtić A, Rodić M, Skodrić-Trifunović V, Marić N, Visekruna J, Spasovski V, Pavlović S. Genomic profiling supports the diagnosis of primary ciliary dyskinesia and reveals novel candidate genes and genetic variants. in PLoS One. 2018;13(10). doi:10.1371/journal.pone.0205422 .
Anđelković, Marina, Minić, Predrag, Vreca, Misa, Stojiljković, Maja, Skakić, Anita, Sovtić, Aleksandar, Rodić, Milan, Skodrić-Trifunović, Vesna, Marić, Nina, Visekruna, Jelena, Spasovski, Vesna, Pavlović, Sonja, "Genomic profiling supports the diagnosis of primary ciliary dyskinesia and reveals novel candidate genes and genetic variants" in PLoS One, 13, no. 10 (2018), https://doi.org/10.1371/journal.pone.0205422 . .