From the Guidelines
The answer is A. Allelic heterogeneity, as it describes a situation where multiple different mutations in the same gene can cause the same disease phenotype, which is exactly what happens in cystic fibrosis 1. In cystic fibrosis, over 1,000 different mutations have been identified in the CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) gene, all leading to the clinical manifestations of cystic fibrosis. These mutations can include deletions, missense mutations, nonsense mutations, and splicing defects, but they all affect the same gene and result in the same disease.
Key Points
- The CFTR gene is located on the long arm of chromosome 7 in humans 1
- CFTR is an apical membrane Cl− channel that controls epithelial fluid and salt secretion, where mutations in CFTR lead to dehydrated, acidic secretions, which drive CF disease 1
- The most commonly reported mutation results from a phenylalanine deletion at position 508 (F508del), with at least one allelic copy of this mutation present in 70–90% of patients with CF 1
Comparison to Other Concepts
This differs from:
- Locus heterogeneity (where mutations in different genes cause the same disease)
- Codominance (where both alleles are fully expressed in heterozygotes)
- Epistasis (where one gene affects the expression of another)
- Linkage (which describes the tendency of genes located close together on a chromosome to be inherited together) As stated in the study published in Diabetologia in 2016, CF is an autosomal recessive disorder caused by mutations in the CFTR gene 1.
Clinical Implications
Understanding the concept of allelic heterogeneity is crucial in the diagnosis and treatment of cystic fibrosis, as it highlights the importance of genetic testing and personalized medicine in managing the disease.
From the Research
Cystic Fibrosis and CFTR Gene Mutations
- The phenomenon of several different mutations in the CFTR gene causing cystic fibrosis can be described by the concept of allelic heterogeneity 2, 3.
- Allelic heterogeneity refers to the presence of different mutations at the same gene locus that can cause the same disease or phenotype.
- In the case of cystic fibrosis, multiple mutations in the CFTR gene have been identified, and these mutations can result in different forms of the disease 4, 5.
- The identification of these mutations is important for understanding the molecular mechanisms of the disease and for developing targeted therapies 6.
Key Findings
- Studies have shown that there are over 2000 known mutations in the CFTR gene that can cause cystic fibrosis 4, 5.
- These mutations can affect the structure and function of the CFTR protein, leading to impaired ion transport and disease pathology 6.
- The concept of allelic heterogeneity is supported by the finding that different mutations in the CFTR gene can result in different clinical phenotypes and disease severities 2, 3.
Implications
- Understanding the concept of allelic heterogeneity in cystic fibrosis is important for developing effective diagnostic and therapeutic strategies 2, 4.
- The identification of specific mutations in the CFTR gene can help guide treatment decisions and improve patient outcomes 5, 6.
- Further research is needed to fully understand the molecular mechanisms of cystic fibrosis and to develop targeted therapies for this disease 3, 6.