Evaluation of the Disease Liability of CFTR Variants

  • Patrick R. Sosnay
  • Carlo Castellani
  • Mary Corey
  • Ruslan Dorfman
  • Julian Zielenski
  • Rachel Karchin
  • Christopher M. Penland
  • Garry R. Cutting
Part of the Methods in Molecular Biology book series (MIMB, volume 742)


Over 1600 novel sequence variants in the CFTR gene have been reported to the CF Mutation Database ( While about 25 mutations are well characterized by clinical studies and functional assays, the disease liability of most of the remaining mutations is either unclear or unknown. This gap in knowledge has implications for diagnosis, therapy selection, and counseling for patients and families carrying an uncharacterized CFTR mutation. This chapter will describe a critical approach to assessing the disease implications of CFTR mutations utilizing clinical data, literature review, functional testing, and bioinformatic in silico methods.

Key words

CFTR mutations CFTR variants CFTR polymorphisms mutation prediction algorithms in silico testing bioinformatic analysis genotype–phenotype relationship 



The authors would like to thank Neeraj Sharma Ph.D. and Barbara Karczeski M.S., M.A. for their critical review of this manuscript. This work was supported by research grants from the US CF Foundation (CUTTING09A and SOSNAY10Q0) and from the National Institute of Health (HL68927 and DK44003).


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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Patrick R. Sosnay
    • 1
  • Carlo Castellani
    • 2
  • Mary Corey
    • 3
  • Ruslan Dorfman
    • 3
  • Julian Zielenski
    • 3
  • Rachel Karchin
    • 4
  • Christopher M. Penland
    • 5
  • Garry R. Cutting
    • 1
  1. 1.McKusick-Nathans Institute of Genetic MedicineJohns Hopkins University School of MedicineBaltimoreUSA
  2. 2.Cystic Fibrosis CentreOspedale Civile MaggioreVeronaItaly
  3. 3.The Hospital for Sick ChildrenUniversity of TorontoTorontoCanada
  4. 4.Department of Biomedical Engineering, Institute for Computational MedicineJohns Hopkins UniversityBaltimoreUSA
  5. 5.Cystic Fibrosis FoundationBethesdaUSA

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