POTENTIAL NEW GENES INVOLVED IN CYSTIC FIBROSIS PHENOTYPE
Конференцијски прилог (Објављена верзија)
Метаподаци
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Background: Cystic fibrosis (CF) is autosomal
recessive disorder characterized by chronic
respiratory problems and poor growth. CF is caused
by defect in transmembrane conductance regulator
(CFTR) protein. CF is diagnosed by sweat chloride
analysis (>60 mmol/L) with the identification of
two CF-causing variants of CFTR gene. With a
longstanding history of CFTR gene analysis, our
laboratory identified several patients with elevated
sweat chloride and clinical manifestations of CF in
whom no CF-causing mutations were detected after
sequencing of whole coding region and testing for
large insertion/deletion of CFTR gene. In order to
elucidate genetic background of conditions that
mimic CF we performed whole exome sequencing
(WES) in two such patients.
Methods: Library preparation was done using
DNA nanoball technology. Produced fastq files
were mapped to hg38. VCF files were generated
using GATK and annotated with InterVar and AnnoVar
tools. Variants filtering for disea...se relevance was done using the following criteria: QC, GnomAD
Allele Frequency, Functional consequences
and phenotype-genotype relationship.
Results: CACNA1H and MUC5B genes were
found to be impaired in both patients. Similar number
of variants predicted to impair protein function
were detected (27 and 25) in each patient. Loss of
function variants were found in 7 and 11 genes,
respectively.
Conclusion: Further assessment of selected
variants will clarify their functional effect and relevance
for the patient’s clinical phenotype. WES
analysis will help identify genetic aspects of disease
and assist in optimal patient management in about
0.01% of patients with elevated sweat chloride and
high clinical suspicion of CF that do not carry any
CF-causing variants.
Кључне речи:
cystic fibrosis / WES / variant assessment / patient management / rare diseasesИзвор:
International Journal of Medical Genetics, 2023, 26, Supplement, 80-80Издавач:
- Macedonian Academy of Sciences and Arts
Напомена:
- ABSTRACT BOOK: “Genetic Diseases from Diagnostics to Prevention and Therapy” October 05-14th Balkan Congress of Human Genetics & 9th Rare Disease SEE Meeting 2023; Skopje, October 05-07, 2023
Институција/група
Institut za molekularnu genetiku i genetičko inženjerstvoTY - CONF AU - Kusić Tisma, Jelena AU - Ušjak, Dušan AU - Mitić, Martina Mia AU - Divac Rankov, Aleksandra PY - 2023 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/2178 AB - Background: Cystic fibrosis (CF) is autosomal recessive disorder characterized by chronic respiratory problems and poor growth. CF is caused by defect in transmembrane conductance regulator (CFTR) protein. CF is diagnosed by sweat chloride analysis (>60 mmol/L) with the identification of two CF-causing variants of CFTR gene. With a longstanding history of CFTR gene analysis, our laboratory identified several patients with elevated sweat chloride and clinical manifestations of CF in whom no CF-causing mutations were detected after sequencing of whole coding region and testing for large insertion/deletion of CFTR gene. In order to elucidate genetic background of conditions that mimic CF we performed whole exome sequencing (WES) in two such patients. Methods: Library preparation was done using DNA nanoball technology. Produced fastq files were mapped to hg38. VCF files were generated using GATK and annotated with InterVar and AnnoVar tools. Variants filtering for disease relevance was done using the following criteria: QC, GnomAD Allele Frequency, Functional consequences and phenotype-genotype relationship. Results: CACNA1H and MUC5B genes were found to be impaired in both patients. Similar number of variants predicted to impair protein function were detected (27 and 25) in each patient. Loss of function variants were found in 7 and 11 genes, respectively. Conclusion: Further assessment of selected variants will clarify their functional effect and relevance for the patient’s clinical phenotype. WES analysis will help identify genetic aspects of disease and assist in optimal patient management in about 0.01% of patients with elevated sweat chloride and high clinical suspicion of CF that do not carry any CF-causing variants. PB - Macedonian Academy of Sciences and Arts C3 - International Journal of Medical Genetics T1 - POTENTIAL NEW GENES INVOLVED IN CYSTIC FIBROSIS PHENOTYPE EP - 80 IS - Supplement SP - 80 VL - 26 UR - https://hdl.handle.net/21.15107/rcub_imagine_2178 ER -
@conference{ author = "Kusić Tisma, Jelena and Ušjak, Dušan and Mitić, Martina Mia and Divac Rankov, Aleksandra", year = "2023", abstract = "Background: Cystic fibrosis (CF) is autosomal recessive disorder characterized by chronic respiratory problems and poor growth. CF is caused by defect in transmembrane conductance regulator (CFTR) protein. CF is diagnosed by sweat chloride analysis (>60 mmol/L) with the identification of two CF-causing variants of CFTR gene. With a longstanding history of CFTR gene analysis, our laboratory identified several patients with elevated sweat chloride and clinical manifestations of CF in whom no CF-causing mutations were detected after sequencing of whole coding region and testing for large insertion/deletion of CFTR gene. In order to elucidate genetic background of conditions that mimic CF we performed whole exome sequencing (WES) in two such patients. Methods: Library preparation was done using DNA nanoball technology. Produced fastq files were mapped to hg38. VCF files were generated using GATK and annotated with InterVar and AnnoVar tools. Variants filtering for disease relevance was done using the following criteria: QC, GnomAD Allele Frequency, Functional consequences and phenotype-genotype relationship. Results: CACNA1H and MUC5B genes were found to be impaired in both patients. Similar number of variants predicted to impair protein function were detected (27 and 25) in each patient. Loss of function variants were found in 7 and 11 genes, respectively. Conclusion: Further assessment of selected variants will clarify their functional effect and relevance for the patient’s clinical phenotype. WES analysis will help identify genetic aspects of disease and assist in optimal patient management in about 0.01% of patients with elevated sweat chloride and high clinical suspicion of CF that do not carry any CF-causing variants.", publisher = "Macedonian Academy of Sciences and Arts", journal = "International Journal of Medical Genetics", title = "POTENTIAL NEW GENES INVOLVED IN CYSTIC FIBROSIS PHENOTYPE", pages = "80-80", number = "Supplement", volume = "26", url = "https://hdl.handle.net/21.15107/rcub_imagine_2178" }
Kusić Tisma, J., Ušjak, D., Mitić, M. M.,& Divac Rankov, A.. (2023). POTENTIAL NEW GENES INVOLVED IN CYSTIC FIBROSIS PHENOTYPE. in International Journal of Medical Genetics Macedonian Academy of Sciences and Arts., 26(Supplement), 80-80. https://hdl.handle.net/21.15107/rcub_imagine_2178
Kusić Tisma J, Ušjak D, Mitić MM, Divac Rankov A. POTENTIAL NEW GENES INVOLVED IN CYSTIC FIBROSIS PHENOTYPE. in International Journal of Medical Genetics. 2023;26(Supplement):80-80. https://hdl.handle.net/21.15107/rcub_imagine_2178 .
Kusić Tisma, Jelena, Ušjak, Dušan, Mitić, Martina Mia, Divac Rankov, Aleksandra, "POTENTIAL NEW GENES INVOLVED IN CYSTIC FIBROSIS PHENOTYPE" in International Journal of Medical Genetics, 26, no. Supplement (2023):80-80, https://hdl.handle.net/21.15107/rcub_imagine_2178 .