Molecular Diagnosis of Cystic Fibrosis

Joshua L. Deignan1, Wayne W. Grody2

1 Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, 2 Divisions of Medical Genetics and Molecular Diagnostics, Departments of Pathology and Laboratory Medicine, Pediatrics, and Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles
Publication Name:  Current Protocols in Human Genetics
Unit Number:  Unit 9.28
DOI:  10.1002/0471142905.hg0928s88
Online Posting Date:  January, 2016
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This unit describes a recommended approach to identifying causal genetic variants in an individual suspected of having cystic fibrosis. An introduction to the genetics and clinical presentation of cystic fibrosis is initially presented, followed by a description of the two main strategies used in the molecular diagnosis of cystic fibrosis: (1) an initial targeted variant panel used to detect only the most common cystic fibrosis‐causing variants in the CFTR gene, and (2) sequencing of the entire coding region of the CFTR gene to detect additional rare causal CFTR variants. Finally, the unit concludes with a discussion regarding the analytic and clinical validity of these approaches. © 2016 by John Wiley & Sons, Inc.

Keywords: cystic fibrosis; CFTR; pancreatic insufficiency; sequencing; CBAVD

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Table of Contents

  • Introduction
  • Strategic Planning
  • Targeted Cystic Fibrosis Variant Panels
  • Assessment of the Entire CFTR Gene
  • Guide to Data Interpretation
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Literature Cited

Literature Cited
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  Massie, J., Castellani, C., and Grody, W.W. 2014. Carrier screening for cystic fibrosis in the new era of medications that restore CFTR function. Lancet Resp. Med. 383:923‐925. doi: 10.1016/S0140-6736(13)61092-2.
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  Richards, C.S., Bradley, L.A., Amos, J., Allitto, B., Grody, W.W., Maddalena, A., McGinnis, M.J., Prior, T.W., Popovich, B.W., Watson, M.S., and Palomaki, G.E. 2002. Standards and guidelines for CFTR mutation testing. Genet Med. 4:379‐391. doi: 10.1097/00125817-200209000-00010.
  Richards, S., Aziz, N., Bale, S., Bick, D., Das, S., Gastier‐Foster, J., Grody, W.W., Hegde, M., Lyon, E., Spector, E., Voelkerding, K., Rehm, H.L., and ACMG Laboratory Quality Assurance Committee. 2015. Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 17:405‐424. doi: 10.1038/gim.2015.30.
  Watson, M.S., Cutting, G.R., Desnick, R.J., Driscoll, D.A., Klinger, K., Mennuti, M., Palomaki, G.E., Popovich, B.W., Pratt, V.M., Rohlfs, E.M., Strom, C.M., Richards, C.S., Witt, D.R., and Grody, W.W. 2004. Cystic fibrosis population carrier screening: 2004 revision of American College of Medical Genetics mutation panel. Genet Med. 6:387‐391. doi: 10.1097/01.GIM.0000139506.11694.7C.
Internet Resource
  The Clinical and Functional TRanslation of CFTR (CFTR2).
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