TY  - JOUR
AU  - Stevanović, Nina
AU  - Skakić, Anita
AU  - Minić, Predrag
AU  - Sovtić, Aleksandar
AU  - Stojiljković, Maja
AU  - Pavlović, Sonja
AU  - Anđelković, Marina
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1456
AB  - 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.
PB  - MDPI, Basel
T2  - International Journal of Molecular Sciences
T1  - Identification and Classification of Novel Genetic Variants: En Route to the Diagnosis of Primary Ciliary Dyskinesia
IS  - 16
VL  - 22
DO  - 10.3390/ijms22168821
ER  - 

@article{
author = "Stevanović, Nina and Skakić, Anita and Minić, Predrag and Sovtić, Aleksandar and Stojiljković, Maja and Pavlović, Sonja and Anđelković, Marina",
year = "2021",
abstract = "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.",
publisher = "MDPI, Basel",
journal = "International Journal of Molecular Sciences",
title = "Identification and Classification of Novel Genetic Variants: En Route to the Diagnosis of Primary Ciliary Dyskinesia",
number = "16",
volume = "22",
doi = "10.3390/ijms22168821"
}

Stevanović, N., Skakić, A., Minić, P., Sovtić, A., Stojiljković, M., Pavlović, S.,& Anđelković, M.. (2021). Identification and Classification of Novel Genetic Variants: En Route to the Diagnosis of Primary Ciliary Dyskinesia. in International Journal of Molecular Sciences
MDPI, Basel., 22(16).
https://doi.org/10.3390/ijms22168821

Stevanović N, Skakić A, Minić P, Sovtić A, Stojiljković M, Pavlović S, Anđelković M. Identification and Classification of Novel Genetic Variants: En Route to the Diagnosis of Primary Ciliary Dyskinesia. in International Journal of Molecular Sciences. 2021;22(16).
doi:10.3390/ijms22168821 .

Stevanović, Nina, Skakić, Anita, Minić, Predrag, Sovtić, Aleksandar, Stojiljković, Maja, Pavlović, Sonja, Anđelković, Marina, "Identification and Classification of Novel Genetic Variants: En Route to the Diagnosis of Primary Ciliary Dyskinesia" in International Journal of Molecular Sciences, 22, no. 16 (2021),
https://doi.org/10.3390/ijms22168821 . .

TY  - JOUR
AU  - Anđelković, Marina
AU  - Spasovski, Vesna
AU  - Vreća, Miša
AU  - Sovtić, Aleksandar
AU  - Rodić, Milan
AU  - Komazec, Jovana
AU  - Pavlović, Sonja
AU  - Minić, Predrag
PY  - 2019
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1260
AB  - Uvod/Cilj Izmenjena funkcija aksonemalne strukture dovodi do ciliopatija (motornih i senzornih), koje su do sada povezane sa brojnim pedijatrijskim poremećajima, uključujući i respiratorne. Primarna cilijarna diskinezija (PCD) najčešća je ciliopatija, koja nastaje kao posledica poremećaja u motornim cilijama. Promenjena struktura i/ ili funkcija motornih cilija dovodi do neonatalnog respiratornog distresa, hroničnog vlažnog kašlja, simptoma nazalne sekrecije, bronhoektazija, hronične upale sinusa i uha, a 50% bolesnika ima i situs inversus. Ovi simptomi su prilično uobičajeni kod male dece i u drugim stanjima; stoga je uspostavljanje precizne dijagnoze otežano. Cilj ovog istraživanja je ukazivanje na značaj genomskog profilisanja bolesnika i dizajniranje strategije za genetičku analizu podataka kod bolesnika suspektnih na ciliopatije sa kliničkom slikom sličnom drugim bolestima pluća. Metode Sproveli smo bioinformatičku analizu podataka dobijenih metodom sekvenciranja nove generacije 21 bolesnika sa potvrđenom ili suspektnom dijagnozom PCD-a. Analizirano je 93 gena: 29 PCD gena, 45 gena asociranih sa pojedinačnim simptomima plućnih bolesti i 19 gena asociranih sa senzornim ciliopatijama. Rezultati Dizajnirani algoritam za genetičku analizu NAM je omogućio da potvrdimo kliničku i uspostavimo genetičku dijagnozu kod 17/21 (80,95%) bolesnika, među kojima je 11/21 (52,38%) PCD bolesnika. Kod 3/21 (14,28%) bolesnika detektovane su monoalelske varijante u PCD genima, kod 6/21 (28,57%) bolesnika detektovane su varijante u genima relevantnim za druga plućna oboljenja, dok je kod 1/21 (4,76%) bolesnika genetička osnovna bolesti ostala nerazjašnjena. Zaključak Dizajniranje strategije za lakše i brže uspostavljanje konačne dijagnoze ciliopatija je obavezno i uključuje i kliničku i genetičku potvrdu bolesti.
AB  - Introduction/Objective Dysfunction of the axonemal structure leads to ciliopathies. Sensory and mo-tile ciliopathies have been associated with numerous pediatric diseases, including respiratory diseases. Primary ciliary dyskinesia (PCD) is ciliopathy linked to the dysfunction of motile cilia. Motile ciliary dys-function in childhood leads to chronic rhinosinusitis, persistent cough, neonatal respiratory distress, bronchiectasis, and situs inversus (SI) have 50% of patients. These symptoms are common among pediatric lung diseases, which additionally makes it difficult to establish the accurate diagnosis. The aim of the study was to point out the significance of genomic profiling for patients with suspected ciliopathies and to design a strategy for genomic analysis relevant for differential diagnosis of lung disease patients with suspected ciliopathies. Methods We conducted a bioinformatic analysis of data generated by New Generation Sequencing (NGS) approach of 21 patients with final or suspected diagnosis of PCD. It was analyzed 93 genes: 29 PCD genes, 45 genes related to individual symptoms of lung diseases, and 19 genes related to sensory ciliopathies. Results the algorithm we have designed, enabled us to establish the clinical and genetic diagnosis for 17/21 (80.95%) patients, among which 11/21 (52.38%) were PCD patients. In 3/21 (14.28%) patients we detected monoallelic variants in PCD disease-causing genes. In 6/21 (28.57%) patients, variants in genes for other pulmonary diseases were detected, and for one patient, genetic background of disease remained unclear. Conclusion an improved strategy for easier and faster establishment of final diagnosis of ciliopathies is mandatory and includes both, clinical and genetic confirmation of disease.
PB  - Srpsko lekarsko društvo, Beograd
T2  - Srpski arhiv za celokupno lekarstvo
T1  - Značaj genomskog profilisanja za diferencijalnu dijagnozu pedijatrijskih bolesnika sa bolestima pluća suspektnih na ciliopatije
T1  - The importance of genomic profiling for differential diagnosis of pediatric lung disease patients with suspected ciliopathies
EP  - 166
IS  - 3-4
SP  - 160
VL  - 147
DO  - 10.2298/SARH181012012A
ER  - 

@article{
author = "Anđelković, Marina and Spasovski, Vesna and Vreća, Miša and Sovtić, Aleksandar and Rodić, Milan and Komazec, Jovana and Pavlović, Sonja and Minić, Predrag",
year = "2019",
abstract = "Uvod/Cilj Izmenjena funkcija aksonemalne strukture dovodi do ciliopatija (motornih i senzornih), koje su do sada povezane sa brojnim pedijatrijskim poremećajima, uključujući i respiratorne. Primarna cilijarna diskinezija (PCD) najčešća je ciliopatija, koja nastaje kao posledica poremećaja u motornim cilijama. Promenjena struktura i/ ili funkcija motornih cilija dovodi do neonatalnog respiratornog distresa, hroničnog vlažnog kašlja, simptoma nazalne sekrecije, bronhoektazija, hronične upale sinusa i uha, a 50% bolesnika ima i situs inversus. Ovi simptomi su prilično uobičajeni kod male dece i u drugim stanjima; stoga je uspostavljanje precizne dijagnoze otežano. Cilj ovog istraživanja je ukazivanje na značaj genomskog profilisanja bolesnika i dizajniranje strategije za genetičku analizu podataka kod bolesnika suspektnih na ciliopatije sa kliničkom slikom sličnom drugim bolestima pluća. Metode Sproveli smo bioinformatičku analizu podataka dobijenih metodom sekvenciranja nove generacije 21 bolesnika sa potvrđenom ili suspektnom dijagnozom PCD-a. Analizirano je 93 gena: 29 PCD gena, 45 gena asociranih sa pojedinačnim simptomima plućnih bolesti i 19 gena asociranih sa senzornim ciliopatijama. Rezultati Dizajnirani algoritam za genetičku analizu NAM je omogućio da potvrdimo kliničku i uspostavimo genetičku dijagnozu kod 17/21 (80,95%) bolesnika, među kojima je 11/21 (52,38%) PCD bolesnika. Kod 3/21 (14,28%) bolesnika detektovane su monoalelske varijante u PCD genima, kod 6/21 (28,57%) bolesnika detektovane su varijante u genima relevantnim za druga plućna oboljenja, dok je kod 1/21 (4,76%) bolesnika genetička osnovna bolesti ostala nerazjašnjena. Zaključak Dizajniranje strategije za lakše i brže uspostavljanje konačne dijagnoze ciliopatija je obavezno i uključuje i kliničku i genetičku potvrdu bolesti., Introduction/Objective Dysfunction of the axonemal structure leads to ciliopathies. Sensory and mo-tile ciliopathies have been associated with numerous pediatric diseases, including respiratory diseases. Primary ciliary dyskinesia (PCD) is ciliopathy linked to the dysfunction of motile cilia. Motile ciliary dys-function in childhood leads to chronic rhinosinusitis, persistent cough, neonatal respiratory distress, bronchiectasis, and situs inversus (SI) have 50% of patients. These symptoms are common among pediatric lung diseases, which additionally makes it difficult to establish the accurate diagnosis. The aim of the study was to point out the significance of genomic profiling for patients with suspected ciliopathies and to design a strategy for genomic analysis relevant for differential diagnosis of lung disease patients with suspected ciliopathies. Methods We conducted a bioinformatic analysis of data generated by New Generation Sequencing (NGS) approach of 21 patients with final or suspected diagnosis of PCD. It was analyzed 93 genes: 29 PCD genes, 45 genes related to individual symptoms of lung diseases, and 19 genes related to sensory ciliopathies. Results the algorithm we have designed, enabled us to establish the clinical and genetic diagnosis for 17/21 (80.95%) patients, among which 11/21 (52.38%) were PCD patients. In 3/21 (14.28%) patients we detected monoallelic variants in PCD disease-causing genes. In 6/21 (28.57%) patients, variants in genes for other pulmonary diseases were detected, and for one patient, genetic background of disease remained unclear. Conclusion an improved strategy for easier and faster establishment of final diagnosis of ciliopathies is mandatory and includes both, clinical and genetic confirmation of disease.",
publisher = "Srpsko lekarsko društvo, Beograd",
journal = "Srpski arhiv za celokupno lekarstvo",
title = "Značaj genomskog profilisanja za diferencijalnu dijagnozu pedijatrijskih bolesnika sa bolestima pluća suspektnih na ciliopatije, The importance of genomic profiling for differential diagnosis of pediatric lung disease patients with suspected ciliopathies",
pages = "166-160",
number = "3-4",
volume = "147",
doi = "10.2298/SARH181012012A"
}

Anđelković, M., Spasovski, V., Vreća, M., Sovtić, A., Rodić, M., Komazec, J., Pavlović, S.,& Minić, P.. (2019). Značaj genomskog profilisanja za diferencijalnu dijagnozu pedijatrijskih bolesnika sa bolestima pluća suspektnih na ciliopatije. in Srpski arhiv za celokupno lekarstvo
Srpsko lekarsko društvo, Beograd., 147(3-4), 160-166.
https://doi.org/10.2298/SARH181012012A

Anđelković M, Spasovski V, Vreća M, Sovtić A, Rodić M, Komazec J, Pavlović S, Minić P. Značaj genomskog profilisanja za diferencijalnu dijagnozu pedijatrijskih bolesnika sa bolestima pluća suspektnih na ciliopatije. in Srpski arhiv za celokupno lekarstvo. 2019;147(3-4):160-166.
doi:10.2298/SARH181012012A .

Anđelković, Marina, Spasovski, Vesna, Vreća, Miša, Sovtić, Aleksandar, Rodić, Milan, Komazec, Jovana, Pavlović, Sonja, Minić, Predrag, "Značaj genomskog profilisanja za diferencijalnu dijagnozu pedijatrijskih bolesnika sa bolestima pluća suspektnih na ciliopatije" in Srpski arhiv za celokupno lekarstvo, 147, no. 3-4 (2019):160-166,
https://doi.org/10.2298/SARH181012012A . .