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Molecular Genetics of Cystic Fibrosis

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Cystic Fibrosis

Part of the book series: Respiratory Medicine ((RM))

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Abstract

Cystic fibrosis is an autosomal recessive condition caused by loss of function of the Cystic Fibrosis Transmembrane conductance Regulator (CFTR). Many different DNA sequence variants can cause CF by affecting a variety of molecular mechanisms. Identifying, classifying, and understanding the mechanistic consequences of pathogenic CFTR variants have long been the primary goals of CF molecular genetics research. The functional consequences of many CFTR variants have been studied utilizing epidemiological studies, detailed clinical studies, and various model organisms and model systems. Capitalizing on the mechanistic understanding of specific pathogenic variants enabled development of small molecule modulators of mutant forms of CFTR. Future modulators will likely also rely on understanding the functional consequences of pathogenic variants to deliver effective molecular therapies to more individuals with CF. At the same time, research into gene therapy continues to progress with the promise of delivering long-term treatment for all individuals with CF. However, CF can be highly variable and individuals with the same CFTR genotype may present with differing severity of phenotype or therapeutic response. Thus, a significant portion of the variability underlying CF lies separate from the disease-causing variant, hidden among cis variation within CFTR as well as trans variation at genetic loci distinct from CFTR. Understanding the total variation contained in the genome of CF patients will allow for a complete understanding of their phenotype, enabling development and delivery of precise medical care for every individual living with CF.

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Authors and Affiliations

  1. Johns Hopkins University School of Medicine, Institute of Genetic Medicine, Baltimore, MD, USA

    Sangwoo T. Han & Garry R. Cutting

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  1. Sangwoo T. Han
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  2. Garry R. Cutting
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Correspondence to Garry R. Cutting .

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Editors and Affiliations

  1. The University of North Carolina at Chapel Hill, Department of Pediatrics, UNC Children’s Hospital, Chapel Hill, NC, USA

    Stephanie Duggins Davis

  2. Department of Pediatrics, University of Washington School of Medicine, Division of Pulmonary and Sleep Medicine, Seattle Children’s Hospital, Seattle, WA, USA

    Margaret Rosenfeld

  3. Department of Pediatrics, Indiana University School of Medicine, Division of Pediatric Pulmonology, Allergy and Sleep Medicine, Riley Hospital for Children at IU Health, Indianapolis, IN, USA

    James Chmiel

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Han, S.T., Cutting, G.R. (2020). Molecular Genetics of Cystic Fibrosis. In: Davis, S., Rosenfeld, M., Chmiel, J. (eds) Cystic Fibrosis. Respiratory Medicine. Humana, Cham. https://doi.org/10.1007/978-3-030-42382-7_23

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