Targeted sequencing reveals complex, phenotype-correlated genotypes in cystic fibrosis

Maxim Ivanov, Alina Matsvay, Olga Glazova, Stanislav Krasovskiy, Mariya Usacheva, Elena Amelina, Aleksandr Chernyak, Mikhail Ivanov, Sergey Musienko, Timofey Prodanov, Sergey Kovalenko, Ancha Baranova, Kamil Khafizov

    Research output: Contribution to journalArticlepeer-review

    16 Citations (Scopus)


    Background: Cystic fibrosis (CF) is one of the most common life-threatening genetic disorders. Around 2000 variants in the CFTR gene have been identified, with some proportion known to be pathogenic and 300 disease-causing mutations have been characterized in detail by CFTR2 database, which complicates its analysis with conventional methods. Methods: We conducted next-generation sequencing (NGS) in a cohort of 89 adult patients negative for p.Phe508del homozygosity. Complete clinical and demographic information were available for 84 patients. Results: By combining MLPA with NGS, we identified disease-causing alleles in all the CF patients. Importantly, in 10% of cases, standard bioinformatics pipelines were inefficient in identifying causative mutations. Class IV-V mutations were observed in 38 (45%) cases, predominantly ones with pancreatic sufficient CF disease; rest of the patients had Class I-III mutations. Diabetes was seen only in patients homozygous for class I-III mutations. We found that 12% of the patients were heterozygous for more than two pathogenic CFTR mutations. Two patients were observed with p.[Arg1070Gln, Ser466] complex allele which was associated with milder pulmonary obstructions (FVC 107 and 109% versus 67%, CI 95%: 63-72%; FEV 90 and 111% versus 47%, CI 95%: 37-48%). For the first time p.[Phe508del, Leu467Phe] complex allele was reported, observed in four patients (5%). Conclusion: NGS can be a more information-gaining technology compared to standard methods. Combined with its equivalent diagnostic performance, it can therefore be implemented in the clinical practice, although careful validation is still required.

    Original languageEnglish
    Article number13
    Pages (from-to)13
    Number of pages12
    JournalBMC Medical Genomics
    Issue numberSuppl 1
    Publication statusPublished - 13 Feb 2018


    • CFTR cystic fibrosis
    • NGS next generation sequencing
    • Cystic Fibrosis Transmembrane Conductance Regulator/deficiency
    • Genetic Association Studies
    • Biomarkers/analysis
    • Humans
    • Middle Aged
    • Male
    • High-Throughput Nucleotide Sequencing/methods
    • Young Adult
    • Adult
    • Female
    • Mutation
    • Cystic Fibrosis/genetics
    • Cohort Studies
    • ORIGIN
    • SERVER


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