LittleLab4CF
Super Moderator
Cystic Fibrosis (CF) is the result of an error in a particular gene on both chromosomes. One copy of our 23 different chromosomes are inherited from each parent which means all the cells in our body have 23 from mom, 23 from dad for a total of 46. CF is an autosomal recessive genetic disease for the most part.* This means two copies of the same mutation must be present for CF to happen. Germ cells, our sperm and eggs only have one set and that's where the next generation plays dice. People with a single CF mutation each are "Carriers". When two carriers commit parenthood, there is a one in four chance baby will inherit both mutations.
The Cystic Fibrosis Transmembrane electrolyte Conductance Regulation (CFTR) gene regulates the electrolyte balance between the inside of cells and the surrounding environment. In spite of having "Cystic Fibrosis" in the name, it normally is a healthy gene and not doing much for most cells in our bodies. The wet surfaces in our bodies, epithelial mucosa or mucus membranes and our skin especially mucus glands and glands with mucus like the thyroid, pancreas, salivary glands, adrenal glands and our reproductive glands have the gene activated. The lungs are a near perfect models for glands. This is where CF can do quick and lethal damage. When two identical copies of a CFTR gene error like DF508 are present, the regulation of chlorine in and out of the cell membranes fails to work properly, or at all. The CFTR gene sets up electrolyte regulation by sending instruction templates from the cell's nucleus to instruct the cell to make ion channels or selective portals on the cell membrane that allow chloride ions to selectively move in and out of the cells.
If a person has CF as I described above, chloride ion channels are not functional, too low in count or location around the cell membrane or the channels work improperly like transport in but not out of the cell. Other electrolyte channels exist for other electrolytes as well as a number of other chemical channels. Sodium chloride, Potassium chloride, Calcium chloride the importance of proper chloride ion exchange is life and death in the worst case. When the salt balance inside a cell is higher than outside the cell, either the cell needs to gain water through osmosis or lose chloride. Because of CF, all the nice thin mucus our mucus cells makes is coming out thick, sticky and desiccated because the mucus cells are swollen with water in an attempt to equalize the salt concentration. Osmosis is a powerful force even if it takes on impossible tasks.
*CF's definition is a moving target as we learn more about CF's genetics and the genetic database vs patient's presentation. For many, CF's genetics being discovered in 1989 sounds like a long time ago. This was barely a discovery, we initially thought CF was essentially 4 mutations and they HAD to be identical like G551D on both chromosomes. The list of mutations kept growing as Ambry Genetics invested in more refined testing. The list grew from a few to ~1900 plus a list of theoretical mutations now that the gene has been sequenced.
CF can easily be two different mutations where G551D could be on one chromosome copy and DF508 on the other. Since both mutations are known bad genes, CF's definition now includes this type of variation. With 1900 X 1900 possible combinations, the expression of CF symptoms can be from no issues to a life lasting just a few days. Carriers used to be considered perfectly healthy because one chromosome has a perfectly functioning CFTR gene that compensates more than enough to be symptom free. Oops! Not all CFTR mutations cause CF, even in pairs and a number of carriers like me, have CF diagnosis from sweat chloride.
In the final analysis, treatment of the issues is the prize to keep your eyes on. CF is not a disease you wish on anybody, especially your child. Until very recent introduction of Kalydeco, a genetic drug that is mutation specific and similar CF genetic drugs in the pipeline, genetic testing was mostly a novelty. Then again, sometimes a diagnosis is reaffirming.
Not every pulmonary problem is going to be CF. Culturing pseudo or steno frequently comes from a contaminated instrument or oxygen cannula, something "hospital acquired" would be the likely source. Finding 5T polymorphisms is kind of sketchy when it comes to CF. Five T (5T) polymorphisms and higher are common. A contributor who is very knowledgeable about CF genetics is adamant that T polymorphisms do not contribute to the disease. I have a doctorate in genetics and if I know anything it is to avoid absolutes, or rules in mammalian genetics. Every rule in human genetics will have exceptions. High count T polymorphisms are often seen in symptomatic carriers. This is not scientifically valid, it is a general observation.
Best wishes and hopefully Ambry will have some answers,
LL
The Cystic Fibrosis Transmembrane electrolyte Conductance Regulation (CFTR) gene regulates the electrolyte balance between the inside of cells and the surrounding environment. In spite of having "Cystic Fibrosis" in the name, it normally is a healthy gene and not doing much for most cells in our bodies. The wet surfaces in our bodies, epithelial mucosa or mucus membranes and our skin especially mucus glands and glands with mucus like the thyroid, pancreas, salivary glands, adrenal glands and our reproductive glands have the gene activated. The lungs are a near perfect models for glands. This is where CF can do quick and lethal damage. When two identical copies of a CFTR gene error like DF508 are present, the regulation of chlorine in and out of the cell membranes fails to work properly, or at all. The CFTR gene sets up electrolyte regulation by sending instruction templates from the cell's nucleus to instruct the cell to make ion channels or selective portals on the cell membrane that allow chloride ions to selectively move in and out of the cells.
If a person has CF as I described above, chloride ion channels are not functional, too low in count or location around the cell membrane or the channels work improperly like transport in but not out of the cell. Other electrolyte channels exist for other electrolytes as well as a number of other chemical channels. Sodium chloride, Potassium chloride, Calcium chloride the importance of proper chloride ion exchange is life and death in the worst case. When the salt balance inside a cell is higher than outside the cell, either the cell needs to gain water through osmosis or lose chloride. Because of CF, all the nice thin mucus our mucus cells makes is coming out thick, sticky and desiccated because the mucus cells are swollen with water in an attempt to equalize the salt concentration. Osmosis is a powerful force even if it takes on impossible tasks.
*CF's definition is a moving target as we learn more about CF's genetics and the genetic database vs patient's presentation. For many, CF's genetics being discovered in 1989 sounds like a long time ago. This was barely a discovery, we initially thought CF was essentially 4 mutations and they HAD to be identical like G551D on both chromosomes. The list of mutations kept growing as Ambry Genetics invested in more refined testing. The list grew from a few to ~1900 plus a list of theoretical mutations now that the gene has been sequenced.
CF can easily be two different mutations where G551D could be on one chromosome copy and DF508 on the other. Since both mutations are known bad genes, CF's definition now includes this type of variation. With 1900 X 1900 possible combinations, the expression of CF symptoms can be from no issues to a life lasting just a few days. Carriers used to be considered perfectly healthy because one chromosome has a perfectly functioning CFTR gene that compensates more than enough to be symptom free. Oops! Not all CFTR mutations cause CF, even in pairs and a number of carriers like me, have CF diagnosis from sweat chloride.
In the final analysis, treatment of the issues is the prize to keep your eyes on. CF is not a disease you wish on anybody, especially your child. Until very recent introduction of Kalydeco, a genetic drug that is mutation specific and similar CF genetic drugs in the pipeline, genetic testing was mostly a novelty. Then again, sometimes a diagnosis is reaffirming.
Not every pulmonary problem is going to be CF. Culturing pseudo or steno frequently comes from a contaminated instrument or oxygen cannula, something "hospital acquired" would be the likely source. Finding 5T polymorphisms is kind of sketchy when it comes to CF. Five T (5T) polymorphisms and higher are common. A contributor who is very knowledgeable about CF genetics is adamant that T polymorphisms do not contribute to the disease. I have a doctorate in genetics and if I know anything it is to avoid absolutes, or rules in mammalian genetics. Every rule in human genetics will have exceptions. High count T polymorphisms are often seen in symptomatic carriers. This is not scientifically valid, it is a general observation.
Best wishes and hopefully Ambry will have some answers,
LL
