Cystic Fibrosis (CF) is a genetic condition that primarily affects the lungs and digestive system. It leads to the production of thick, sticky mucus, which can clog airways and ducts in various organs, causing breathing difficulties and issues with nutrient absorption. This disorder arises from a specific genetic change, meaning individuals are born with the condition.
Understanding Genetic Makeup
A person’s “genotype” describes their specific set of genes. Genes are fundamental units of heredity, made of DNA. DNA (deoxyribonucleic acid) is the hereditary material in nearly every cell, carrying instructions for development and function. These DNA molecules are organized into structures called chromosomes, located within cell nuclei. Humans have 23 pairs of chromosomes, inheriting one copy of each gene from each parent. Genes provide instructions for creating proteins, important for various bodily functions.
The CFTR Gene and Its Variations
Cystic Fibrosis results from variations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. This gene instructs the body to make the CFTR protein, a channel on the surface of cells in organs like the lungs, pancreas, and sweat glands. Normally, this protein regulates chloride ion and water movement across cell membranes, important for producing thin, free-flowing mucus and other fluids.
In Cystic Fibrosis, specific variations occur in both copies of the CFTR gene. These mutations disrupt the CFTR protein’s function, preventing its production, causing malformation, or affecting stability. When the CFTR protein malfunctions, chloride ions cannot move out of cells, leading to water retention and the characteristic thick, sticky mucus and salty sweat associated with CF.
Over 2,000 mutations can occur in the CFTR gene. The most common, F508del, involves deleting three DNA bases, leading to a missing amino acid in the CFTR protein. This mutation is present in approximately 70% of individuals with CF and causes the protein to not reach the cell surface. Different mutations lead to varying degrees of protein dysfunction, influencing disease severity.
How Cystic Fibrosis is Inherited
Cystic Fibrosis follows an autosomal recessive inheritance pattern. An individual must inherit two mutated CFTR gene copies—one from each parent—to develop the condition. Inheriting one mutated and one normal copy makes a person a “carrier” of the CF gene. Carriers do not exhibit symptoms because their single functional gene copy produces enough CFTR protein for normal bodily functions.
When both parents are CFTR gene carriers, their children have specific inheritance probabilities. Each child has a 25% chance of inheriting two mutated genes and having Cystic Fibrosis. A 50% chance exists for inheriting one mutated and one normal gene, becoming a carrier like their parents. Finally, there is a 25% chance of inheriting two normal CFTR genes, meaning they will neither have CF nor be a carrier. These probabilities apply to each pregnancy independently.
Identifying the CF Genotype
Identifying a person’s CF genotype involves genetic testing. This testing looks for specific CFTR gene mutations. Genetic testing can be performed in several contexts: newborn screening, carrier screening, and diagnostic testing.
Newborn screening, conducted shortly after birth via a heel prick blood sample, commonly identifies potential CF cases. If positive, further tests like a sweat chloride test and additional genetic tests confirm the diagnosis. Carrier screening helps prospective parents determine if they carry a CFTR gene mutation, informing family planning. Diagnostic testing is also used for individuals exhibiting Cystic Fibrosis symptoms. Genetic counseling provides support and information regarding test results and their implications.