Current and future diagnosis of cystic fibrosis: Performance and limitations
1Laboratoire de Génétique et Biologie Moléculaires, Hôpital Cochin, APHP. Centre Université de Paris, Paris.
Insights
Cystic fibrosis (CF) diagnosis is evolving due to newborn screening, identifying the disorder in infants before symptoms appear. This review details methods for detecting CFTR protein dysfunction and genetic variants to improve patient care.
Area of Science:
- Medical Genetics
- Molecular Biology
- Pediatrics
Background:
- Cystic fibrosis (CF) is a prevalent genetic disorder in Caucasians, frequently indicated for genetic diagnosis.
- Advances in diagnostic techniques have significantly enhanced understanding of CFTR genetics and CF pathophysiology.
- Newborn screening for CF is increasingly implemented, leading to earlier diagnosis in asymptomatic infants.
Purpose of the Study:
- To review current and emerging methods for detecting CFTR protein dysfunction.
- To describe molecular approaches for identifying disease-causing CFTR variants.
- To discuss how improved diagnostic resources can enhance patient care and therapeutic decisions.
Main Methods:
- Review of diagnostic techniques for CFTR protein dysfunction.
- Analysis of molecular approaches for CFTR variant identification.
- Examination of updated European and US guidelines for CF diagnosis.
Main Results:
- Newborn screening has shifted CF diagnosis to asymptomatic infants, altering diagnostic criteria.
- Recent guideline reforms in Europe and the US address sweat chloride values and disease terminology.
- Various functional and genetic methods are available for detecting CFTR dysfunction and variants.
Conclusions:
- Improved understanding of CFTR genetics and pathophysiology aids diagnosis.
- Updated diagnostic guidelines reflect advancements in CF detection.
- Optimal utilization of genetic and functional data can significantly improve CF patient management and treatment strategies.
Abstract:
Cystic fibrosis (CF) is the most frequent genetic disorder in the Caucasian population benefiting from systematic newborn screening tests. It is also the most frequent indication of prenatal and preimplantation genetic diagnosis for a single gene disorder. During the past thirty years, thanks in part to the evolution of diagnostic techniques, our knowledge on CFTR genetics and pathophysiological mechanisms involved in CF have significantly improved. With the implementation of newborn screening in France and in several countries, the diagnosis now often occurs in clinically asymptomatic infants and this has modified the criteria for CF diagnosis. Recently, guidelines for CF diagnosis have been reformulated in Europe and the US, in regard to sweat chloride usual values and disease terminology. This review describes the methods and molecular approaches that are used in routine practice or are being developed to detect CFTR protein dysfunction and to identify disease-causing CFTR variants. Ultimately, an optimal use of all these functional and genetic resources may improve patient care and therapeutic decision-making. © 2020 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.
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