Genomic profiling supports the diagnosis of primary ciliary dyskinesia and reveals novel candidate genes and genetic variants

Autor: Maja Stojiljkovic, Anita Skakic, Jelena Visekruna, Vesna Spasovski, Vesna Skodric-Trifunovic, Predrag Minic, Nina Maric, Misa Vreca, Aleksandar Sovtic, Sonja Pavlovic, Marina Andjelkovic, Milan Rodic
Rok vydání: 2018
Předmět:
0301 basic medicine
Male
Candidate gene
Gene Identification and Analysis
lcsh:Medicine
Compound heterozygosity
Pathology and Laboratory Medicine
Biochemistry
Cohort Studies
Database and Informatics Methods
0302 clinical medicine
Medicine and Health Sciences
lcsh:Science
Child
Frameshift Mutation
Primary ciliary dyskinesia
Genetics
Multidisciplinary
Cilium
Messenger RNA
High-Throughput Nucleotide Sequencing
3. Good health
Nucleic acids
Child
Preschool
Microtubule Proteins
Female
Cellular Structures and Organelles
Pathogens
Microtubule-Associated Proteins
Sequence Analysis
Research Article
Adult
Pathogen Motility
Adolescent
Bioinformatics
Virulence Factors
Biology
Research and Analysis Methods
Frameshift mutation
03 medical and health sciences
Young Adult
Genetic variation
medicine
otorhinolaryngologic diseases
Humans
Cilia
Gene
Mutation Detection
Kartagener Syndrome
lcsh:R
Genetic Variation
Infant
Biology and Life Sciences
Human Genetics
Axonemal Dyneins
Sequence Analysis
DNA
Cell Biology
medicine.disease
Human genetics
Protein Structure
Tertiary
030104 developmental biology
030228 respiratory system
Genetics of Disease
Mutation
RNA
lcsh:Q
Sequence Alignment
Zdroj: PLoS ONE
PLoS ONE, Vol 13, Iss 10, p e0205422 (2018)
ISSN: 1932-6203
Popis: 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.
Databáze: OpenAIRE
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