Cystic fibrosis

Cystic fibrosis
Classifications and external resources
ICD-10 E84.
ICD-9 277
OMIM 219700
DiseasesDB 3347
MedlinePlus 000107
eMedicine ped/535 

Cystic fibrosis (CF) is a common hereditary disease that affects the entire body, causing progressive disability and early death. Difficulty breathing is the most common symptom and results from frequent lung infections, which are treated, though not always cured, by antibiotics and other medications. A multitude of other symptoms, including sinus infections, poor growth, diarrhea, and infertility result from the effects of CF on other parts of the body.

CF is one of the most common fatal inherited diseases. It is most prevalent among Europeans and Ashkenazi Jews; one in twenty-two people of European descent carries one gene for CF, making it the most common genetic disease among them. Individuals with cystic fibrosis can be diagnosed prior to birth by genetic testing or in early childhood by a sweat test. There is no cure for CF, and most individuals with cystic fibrosis die young — many in their 20s and 30s from lung failure. Ultimately, lung transplantation is often necessary as CF worsens.

CF is caused by a mutation in a gene called the cystic fibrosis transmembrane conductance regulator (CFTR). The product of this gene helps create sweat, digestive juices, and mucus. Although most people without CF have two working copies of the CFTR gene, only one is needed to prevent cystic fibrosis. CF develops when neither gene works normally. Therefore, CF is considered an autosomal recessive disease. The name cystic fibrosis refers to the characteristic scarring (fibrosis) and cyst formation within the pancreas, first recognized in the 1930s.[1]



Symptoms and signs

The symptoms of cystic fibrosis depend on the age of an individual, the extent the disease affects specific organs, prior therapy, and the types of infections experienced. Cystic fibrosis affects the entire body and impacts growth, breathing, digestion, and reproduction. The newborn period may be marked by poor weight gain and intestinal blockage caused by thick feces. Other symptoms of CF appear during the remainder of childhood and early adulthood. These include continued problems with growth, the onset of lung disease, and increasing difficulties with poor absorption of vitamins and nutrients by the gastrointestinal tract. In addition, difficulties with fertility may become apparent when reproduction is attempted.


Lung and sinus disease

Lung disease results from clogging of airways due to inflammation. Inflammation and infection cause injury to the lungs and structural changes that lead to a variety of symptoms. In the early stages, incessant coughing, copious phlegm production, and decreased ability to exercise are common. Many of these symptoms occur when bacteria that normally inhabit the thick mucus grow out of control and cause pneumonia. In later stages of CF, changes in the architecture of the lung further exacerbate chronic difficulties in breathing.

Aspergillus fumigatus - A common fungus which can lead to worsening lung disease in people with CF
Aspergillus fumigatus - A common fungus which can lead to worsening lung disease in people with CF

Other symptoms include coughing up blood, changes in the major airways in the lungs (bronchiectasis), high blood pressure in the lung (pulmonary hypertension), heart failure, difficulties getting enough oxygen to the body, and respiratory failure requiring support with breathing masks such as bilevel positive airway pressure machines or ventilators.[2] In addition to typical bacterial infections, people with CF more commonly develop other types of lung disease. Among these is allergic bronchopulmonary aspergillosis, in which the body's response to the common fungus Aspergillus fumigatus causes worsening of breathing problems. Another is infection with mycobacterium avium complex (MAC), a group of bacteria related to tuberculosis which can cause further lung damage and does not respond to common antibiotics.

Mucus in the paranasal sinuses is equally thick and may also cause blockage of the sinus passages, leading to infection. This may cause facial pain, fever, nasal drainage, and headaches. Individuals with CF may develop overgrowth of the nasal tissue (nasal polyps) due to inflammation from chronic sinus infections These polyps can block the nasal passages and increase breathing difficulties.[3][4]


Gastrointestinal, liver and pancreatic disease

Prior to prenatal and newborn screening, cystic fibrosis was often diagnosed when a newborn infant failed to pass feces (meconium). Meconium may completely block the intestines and cause serious illness. This condition, called meconium ileus, occurs in 10% of newborns with CF.[5] In addition, protrusion of internal rectal membranes (rectal prolapse) is more common in CF because of increased fecal volume, malnutrition, and increased intra–abdominal pressure due to coughing.[6]

The thick mucus seen in the lung has its counterpart in thickened secretions from the pancreas, an organ responsible for providing digestive juices which help break down food. These secretions block the movement of the digestive enzymes into the gut and result in irreversible damage to the pancreas, often with painful inflammation (pancreatitis).[7] The lack of digestive enzymes leads to difficulty absorbing nutrients with their subsequent excretion in the feces, a disorder known as malabsorption. Malabsorption leads to malnutrition and poor growth and development because of calorie loss. Individuals with CF also have difficulties absorbing the fat-soluble vitamins A, D, E, and K. In addition to the pancreas problems, people with cystic fibrosis experience more heartburn, intestinal blockage by intussusception, and constipation.[8] Older individuals with CF may also develop distal intestinal obstruction syndrome when thickened feces cause intestinal blockage.[9]

Thickened secretions also may cause liver problems in patients with CF. Bile secreted by the liver to aid in digestion may block the bile ducts, leading to liver damage. Over time, this can lead to cirrhosis, in which the liver fails to clean the blood of toxins and does not make important proteins such as those responsible for blood clotting.[10]


Endocrine disease and growth

Clubbing - Patients with CF often have enlargement of their fingers, as shown here.
Clubbing - Patients with CF often have enlargement of their fingers, as shown here.

The pancreas contains the islets of Langerhans, which are responsible for making insulin, a hormone that helps regulate blood glucose. Damage of the pancreas can lead to loss of the islet cells, leading to diabetes.[11] Vitamin D is involved in calcium and phosphorus regulation. Poor uptake of vitamin D from the diet because of malabsorption leads to the bone disease osteoporosis in which weakened bones are more susceptible to fractures.[12] In addition, people with CF often develop clubbing of their fingers and toes due to the effects of chronic illness and low oxygen on their bones.

Poor growth is a hallmark of CF. Children with CF typically do not gain weight or height at the same rate as their peers and occasionally are not diagnosed until investigation is initiated for poor growth. The causes of growth failure are multi–factorial and include chronic lung infection, poor absorption of nutrients through the gastrointestinal tract, and increased metabolic demand due to chronic illness.



Infertility affects both men and women. At least 97 percent of men with cystic fibrosis are infertile.[13] These men make normal sperm but are missing the tube (vas deferens) which connects the testes to the ejaculatory ducts of the penis.[14] Many men found to have congenital absence of the vas deferens during evaluation for infertility have a mild, previously undiagnosed form of CF.[15] Some women have fertility issues due to thickened cervical mucus or malnutrition. In severe cases, malnutrition disrupts ovulation and causes amenorrhea.[16]


Diagnosis and monitoring

Cystic fibrosis may be diagnosed by newborn screening, sweat testing, or genetic testing. As of 2006 in the United States, ten percent of cases are diagnosed shortly after birth as part of newborn screening programs. The newborn screen identifies increased amounts of the enzyme trypsin. However, most states and countries do not screen for CF routinely at birth. Therefore, most individuals are diagnosed after symptoms prompt an evaluation for cystic fibrosis. The most commonly used form of testing is the sweat test. Sweat testing involves application of a medication that stimulates sweating (pilocarpine) to one electrode of an apparatus and running electric current to a separate electrode on the skin. This process, called iontophoresis, causes sweating; the sweat is then collected on filter paper or in a capillary tube and analyzed for abnormal amounts of sodium and chloride. People with CF have increased amounts of sodium and chloride in their sweat. CF can also be diagnosed by identification of mutations in the CFTR gene.[17]

A multitude of tests is used to identify complications of CF and to monitor disease progression. X-rays and CAT scans are used to examine the lungs for signs of damage or infection. Examination of the sputum under a microscope is used to identify which bacteria are causing infection so that effective antibiotics can be given. Pulmonary function tests measure how well the lungs are functioning, and are used to measure the need for and response to antibiotic therapy. Blood tests can identify liver problems, vitamin deficiencies, and the onset of diabetes. DEXA scans can screen for osteoporosis and testing for fecal elastase can help diagnose insufficient digestive enzymes.


Prenatal diagnosis

Couples who are pregnant or who are planning a pregnancy can themselves be tested for CFTR gene mutations to determine the likelihood that their child will be born with cystic fibrosis. Testing is typically performed first on one or both parents and, if the risk of CF is found to be high, testing on the fetus can then be performed. Because prenatal diagnosis does not allow for better or different treatment of children with CF, the main reason for testing is to offer abortion if the fetus is found to have CF. Cystic fibrosis testing is offered to many couples in the US.[18] The American College of Obstetricians and Gynecologists recommends testing for couples who have a personal or close family history of CF as well as couples at high risk because of their ethnicity.[19]

Because development of CF in the fetus requires each parent to pass on a mutated copy of the CFTR gene and because CF testing is expensive, testing is often performed on just one parent initially. If that parent is found to be a carrier of a CFTR gene mutation, the other parent is then tested to calculate the risk that their children will have CF. CF can result from more than a thousand different mutations and, as of 2006, it is not possible to test for each one. Testing analyzes the blood for the most common mutations such as ΔF508 — most commercially available tests look for 32 or fewer different mutations. If a family has a known uncommon mutation, specific screening for that mutation can be performed. Because not all known mutations are found on current tests, a negative screen does not guarantee that a child will not have CF.[20] In addition, because the mutations tested are necessarily those most common in the highest risk groups, testing in lower risk ethnicities is less successful because the mutations commonly seen in these groups are less common in the general population.

Couples who are at high risk for having a child with CF will often opt to perform further testing before or during pregnancy. In vitro fertilization with preimplantation genetic diagnosis offers the possibility to examine the embryo prior to its placement into the uterus. The test, performed 3 days after fertilization, looks for the presence of abnormal CF genes. If two mutated CFTR genes are identified, the embryo is excluded from embryo transfer and an embryo with at least one normal gene is implanted.

During pregnancy, testing can be performed on the placenta (chorionic villus sampling) or the fluid around the fetus (amniocentesis). However, chorionic villus sampling has a risk of fetal death of 1 in 100 and amniocentesis of 1 in 200,[21] so the benefits must be determined to outweigh these risks prior to going forward with testing. Alternatively, some couples choose to undergo third party reproduction with egg or sperm donors.



Cystic fibrosis occurs when there is a mutation in the CFTR gene. The protein created by this gene is anchored to the outer membrane of cells in the sweat glands, lung, pancreas, and other affected organs. The protein spans this membrane and acts as a channel connecting the inner part of the cell (cytoplasm) to the surrounding fluid. This channel is primarily responsible for controlling the movement of chloride from outside the cell into the cell. When the CFTR protein does not work, chloride is trapped outside the cell. Because chloride is negatively charged, positively charged ions also cannot cross into the cell because they are affected by the electrical attraction of the chloride ions. Sodium is the most common ion in the extracellular space and the combination of sodium and chloride creates the salt which is lost in high amounts in the sweat of individuals with CF. This lost salt forms the basis for the sweat test.[2]

How this malfunction of cells in cystic fibrosis causes the clinical manifestations of CF is not well understood. One theory suggests that the lack of chloride absorption through the CFTR protein leads to the accumulation of nutrient–rich mucus in the lungs which allows bacteria to hide from the body's immune system. Another theory proposes that the CFTR protein failure leads to a paradoxical increase in sodium and chloride uptake, which, by leading to increased water reabsorption, creates dehydrated and thick mucus. Yet another theory focuses on abnormal chloride movement out of the cell, which also leads to dehydration of mucus, pancreatic secretions, biliary secretions, etc. These theories all support the observation that the majority of the damage in CF is due to blockage of the narrow passages of affected organs with thickened secretions. These blockages lead to remodeling and infection in the lung, damage by accumulated digestive enzymes in the pancreas, blockage of the intestines by thick feces, etc.[2]


The role of chronic infection in lung disease

The lungs of individuals with cystic fibrosis are colonized and infected by bacteria from an early age. These bacteria, which often spread amongst individuals with CF, thrive in the altered mucus, which collects in the small airways of the lungs. This mucus encourages the development of bacterial microenvironments (biofilms) that are difficult for immune cells (and antibiotics) to penetrate. The lungs respond to repeated damage by thick secretions and chronic infections by gradually remodeling the lower airways (bronchiectasis), making infection even more difficult to eradicate.[22]

Over time, both the types of bacteria and their individual characteristics change in individuals with CF. Initially, common bacteria such as Staphylococcus aureus and Hemophilus influenzae colonize and infect the lungs. Eventually, however, Pseudomonas aeruginosa (and sometimes Burkholderia cepacia) dominates. Once within the lungs, these bacteria adapt to the environment and develop resistance to commonly used antibiotics. Pseudomonas can develop special characteristics which allows the formation of large colonies — these strains are known as "mucoid" Pseudomonas and are rarely seen in people who do not have CF.[22]

One way in which infection has spread is by passage between different individuals with CF.[23] In the past, people with CF often participated in summer "CF Camps" and other recreational gatherings.[24][25] Hospitals grouped patients with CF into common areas and routine equipment (such as nebulizers)[26] was not sterilized between individual patients.[27] This led to transmission of more dangerous strains of bacteria among groups of patients. As a result, individuals with CF are routinely isolated from one another in the health care setting and health care providers are encouraged to wear gowns and gloves when examining patients with CF in order to limit the spread of virulent bacterial strains.[28] Often, patients with particularly damaging bacteria will attend clinics on different days and in different buildings than those without these infections.


Molecular biology

CFTR protein - Molecular structure of the CFTR protein
CFTR protein - Molecular structure of the CFTR protein

The CFTR gene is found at the q31.2 locus of chromosome 7, is 180,000 base pairs long, and creates a protein which is 1,480 amino acids long. The most common mutation, ΔF508 is a deletion (Δ) of three nucleotides that results in a loss of the amino acid phenylalanine (F) at the 508th (508) position on the protein. This mutation accounts for seventy percent of CF worldwide and ninety percent of cases in the United States. There are over 1,400 other mutations which can produce CF, however. In Caucasian populations, the frequency of mutations is as follows:[29]

Mutation Frequency
ΔF508 66.0%
G542X 2.4%
G551D 1.6%
N1303K 1.3%
W1282X 1.2%

There are several mechanisms by which these mutations cause problems with the CFTR protein. ΔF508, for instance, creates a protein which does not fold normally and is degraded by the cell. Several mutations which are common in the Ashkenazi Jewish population result in proteins that are too short because production is ended prematurely. Less common mutations produce proteins that do not use energy normally, do not allow chloride to cross the membrane appropriately, or are degraded at a faster rate than normal. Mutations may also lead to fewer copies of the CFTR protein being produced.[2]

The location of the CFTR gene on chromosome 7
The location of the CFTR gene on chromosome 7

Structurally, CFTR is a type of gene known as an ABC gene.[2] Its protein possesses two ATP-hydrolyzing domains which allows the protein to use energy in the form of ATP. It also contains two domains comprised of 6 alpha helices apiece which allow the protein to cross the cell membrane. A regulatory binding site on the protein allows activation by phosphorylation, mainly by cAMP-dependent protein kinase.[2] The carboxyl terminal of the protein is anchored to the cytoskeleton by a PDZ domain interaction.[30]



A typical breathing treatment for cystic fibrosis, using a mask nebulizer and the ThAIRapy Vest
A typical breathing treatment for cystic fibrosis, using a mask nebulizer and the ThAIRapy Vest

The most consistent aspect of therapy in cystic fibrosis is limiting and treating the lung damage caused by thick mucus and infection with the goal of maintaining quality of life. Intravenous, inhaled, and oral antibiotics are used to treat chronic and acute infections. Mechanical devices and inhalational medications are used to alter and clear the thickened mucus. Other aspects of CF therapy involve treatment of diabetes with insulin, pancreatic disease with enzyme replacement, and infertility with advanced reproductive techniques. In addition, therapies such as transplantation and gene therapy aim to cure some of the effects of cystic fibrosis.


Antibiotics to treat lung disease

Antibiotics are given whenever pneumonia is suspected or there has been a decline in lung function. Antibiotics are often chosen based on information about prior infections. Many bacteria common in cystic fibrosis are resistant to multiple antibiotics and require weeks of treatment with intravenous antibiotics such as vancomycin, tobramycin, meropenem, ciprofloxacin, and piperacillin. This prolonged therapy often necessitates hospitalization and insertion of a more permanent IV such as a PICC line or Port-a-Cath. Inhaled therapy with antibiotics such as tobramycin and colistin is often given for months at a time in order to improve lung function by impeding the growth of colonized bacteria.[31][32] Oral antibiotics such as ciprofloxacin or azithromycin are sometimes given to help prevent infection or to control ongoing infection.[33] Some individuals spend years between hospitalizations for antibiotics, while others require several antibiotic treatments each year.

Several common antibiotics such as tobramycin and vancomycin can cause hearing loss or kidney problems with long-term use. In order to prevent these side effects, the amount of antibiotics in the blood are routinely measured and adjusted accordingly.


Other methods to treat lung disease

Several mechanical techniques are used to dislodge sputum and encourage its expectoration. In the hospital setting, physical therapy is utilized; a therapist pounds an individual's chest with his or her hands several times a day. Devices that recreate this percussive therapy include the ThAIRapy Vest and the intrapulmonary percussive ventilator (IPV). These are portable and adapted for home use.[34] Aerobic exercise is of great benefit to people with cystic fibrosis. Not only does exercise increase sputum clearance, but it improves cardiovascular and overall health.

Aerosolized medications which help loosen secretions include dornase alfa and hypertonic saline.[35] Dornase is a recombinant human deoxyribonuclease which breaks down DNA in the sputum, thus decreasing its viscosity.[36] N-Acetylcysteine may also decrease sputum viscosity, but research and experience have shown its benefits to be minimal. Albuterol and ipratropium bromide are inhaled to increase the size of the small airways by relaxing the surrounding muscles.

As lung disease worsens, breathing support from machines may become necessary. Individuals with CF may need to wear special masks at night that help push air into their lungs. These machines, known as bilevel positive airway pressure (BiPAP) ventilators, help prevent low blood oxygen levels during sleep. BiPAP may also be used during physical therapy to improve sputum clearance.[37] During severe illness, people with CF may need to have a tube placed in their throats and their breathing supported by a ventilator.


Treatment of other aspects of CF

Intracytoplasmic sperm injection is used to provide fertility for men with cystic fibrosis.
Intracytoplasmic sperm injection is used to provide fertility for men with cystic fibrosis.

Newborns with meconium ileus typically require surgery while adults with distal intestinal obstruction syndrome typically do not. Treatment of pancreatic insufficiency by replacement of missing digestive enzymes allows the gut to properly absorb nutrients and vitamins that would otherwise be lost in the feces. Even so, most individuals with CF take additional amounts of vitamins A, D, E, and K and eat high calorie meals. It should be noted, however, that nutritional advice given to patients is, at best, mixed: often, literature encourages the eating of high-fat foods without differentiating between saturated and unsaturated fats/trans-fats: this lack of clear information runs counter to health advice given to the general population, and creates the risk of further serious health problems for people with cystic fibrosis as they grow older. So far, no large-scale research has been carried out into the incidence of atherosclerosis and coronary heart disease in adults with cystic fibrosis.

The diabetes common in CF is typically treated with insulin injections.[38] Development of osteoporosis can be prevented by increased intake of vitamin D and calcium and can be treated by bisphosphonates.[39] Poor growth may be avoided by insertion of a feeding tube for increasing calories through supplemental feeds or by administration of injected growth hormone.[40]

Sinus infections are treated by prolonged courses of antibiotics. The development of nasal polyps or other chronic changes within the nasal passages may severely limit airflow through the nose. Sinus surgery is often used to alleviate nasal obstruction and to limit further infections. Nasal steroids such as fluticasone are used to decrease nasal inflammation.[41] Female infertility may be overcome by assisted reproduction technology, particularly embryo transfer techniques. Male infertility may be overcome with intracytoplasmic sperm injection.[42] Third party reproduction is also a possibility for women with CF.


Transplantation and gene therapy

Lung transplantation often becomes necessary for individuals with cystic fibrosis as lung function and exercise tolerance declines. Although single lung transplantation is possible in other diseases, individuals with CF must have both lungs replaced because the remaining lung would contain bacteria that could infect the transplanted lung. A pancreatic or liver transplant may be performed at the same time in order to alleviate liver disease and/or diabetes.[43] Lung transplantation is considered when lung function approaches a point where it threatens survival or requires assistance from mechanical devices.[44]

Gene therapy holds promise as a potential avenue to cure cystic fibrosis. Gene therapy attempts to place a normal copy of the CFTR gene into affected cells. Studies have shown that to prevent the lung manifestations of cystic fibrosis, only 5–10% the normal amount of CFTR gene expression is needed.[45] Many approaches have been theorized and several clinical trials have been initiated but, as of 2006, many hurdles still exist before gene therapy can be successful.[46]



CF is inherited in an autosomal recessive fashion.
CF is inherited in an autosomal recessive fashion.

Cystic fibrosis is the most common life-limiting autosomal recessive disease among people of European heritage. In the United States, approximately 30,000 individuals have CF; most are diagnosed by six months of age. Canada has approximately 3,000 citizens with CF. Approximately 1 in every 25 people of European descent and 1 in every 29 people of Ashkenazi Jewish descent is a carrier of a cystic fibrosis mutation. Although CF is less common in these groups, approximately 1 in every 46 Hispanics, 1 in every 65 Africans and 1 in every 90 Asians carry at least one abnormal CFTR gene.[47][48][49]

Cystic fibrosis is diagnosed in males and females equally. For unclear reasons, males tend to have a longer life expectancy than females.[50] Life expectancy for people with CF depends largely upon access to health care. In 1959, the median age of survival of children with cystic fibrosis was 6 months. In the United States, the life expectancy for infants born in 2006 with CF is 36.8 years, based upon data compiled by the Cystic Fibrosis Foundation.[51] Similarly, in much of the western world people with CF live to a similar age. However, the life expectancy in underdeveloped countries is much less — the majority of individuals with CF do not live past the age of ten.

The Cystic Fibrosis Foundation also compiles lifestyle information about American adults with CF. In 2004, the foundation reported that 91% had graduated high school and 54% had at least some college education. Employment data revealed 12.6% of adults were disabled and 9.9% were unemployed. Marital information showed that 59% of adults were single and 36% were married or living with a partner. In 2004, 191 American women with CF were pregnant.[52]


Theories about the prevalence of CF

The ΔF508 mutation is estimated to be up to 52,000 years old.[53] Numerous hypotheses have been advanced as to why such a lethal mutation has persisted and spread in the human population. Other common autosomal recessive diseases such as sickle cell anemia have been found to protect carriers from other diseases, a concept known as heterozygote advantage. With the discovery that cholera toxin requires normal host CFTR proteins to function properly, it was hypothesized that carriers of mutant CFTR genes benefited from resistance to cholera and other causes of diarrhea.[54] Further studies have not confirmed this hypothesis.[55][56]

Normal CFTR proteins are also essential for the entry of Salmonella typhi into cells,[57] suggesting that carriers of mutant CFTR genes might be resistant to typhoid fever. No in vivo study has yet confirmed this. In both cases, the low level of cystic fibrosis outside of Europe, in places where both cholera and typhoid fever are endemic, is not immediately explicable.



National Library of Medicine picture of Dorothy Hansine Andersen. Andersen first described cystic fibrosis of the pancreas.
National Library of Medicine picture of Dorothy Hansine Andersen. Andersen first described cystic fibrosis of the pancreas.

Although the entire clinical spectrum of CF was not recognized until the 1930s, certain aspects of CF were identified much earlier. Indeed, literature from Germany and Switzerland in the 1700s warned "Wehe dem Kind, das beim Kuß auf die Stirn salzig schmekt, er ist verhext und muss bald sterben" which translates to "Woe is the child who tastes salty from a kiss on the brow, for he is cursed, and soon must die," recognizing the association between the salt loss in CF and illness. Carl von Rokitansky described a case of fetal death with meconium peritonitis, a complication of meconium ileus associated with cystic fibrosis. Meconium ileus was first described in 1905 by Karl Landsteiner.[58] In 1936, Guido Fanconi published a paper describing a connection between celiac disease, cystic fibrosis of the pancreas, and bronchiectasis.[59]

In 1938, Dorothy Hansine Andersen published an article titled "Cystic fibrosis of the pancreas and its relation to celiac disease: a clinical and pathological study" in the American Journal of Diseases of Children. In her paper, she described the characteristic cystic fibrosis of the pancreas correlated it with the lung and intestinal disease prominent in CF.[1] She also first hypothesized that CF was a recessive disease and first used pancreatic enzyme replacement to treat affected children. In 1952, Paul di Sant' Agnese discovered abnormalities in sweat electrolytes; the sweat test was developed and improved over the next decade.[60]

In 1988, the first mutation for CF, ΔF508, was discovered by Francis Collins, Lap-Chee Tsui and John R. Riordan on the seventh chromosome. Research has subsequently found over 1000 different mutations that cause CF. Lap-Chee Tsui led a team of researchers at the Hospital for Sick Children in Toronto that discovered the gene responsible for CF in 1989. Cystic fibrosis represents the first genetic disorder elucidated strictly by the process of reverse genetics. Because mutations in the CFTR gene are typically small, classical genetics techniques were not able to accurately pinpoint the mutated gene.[61] Using protein markers, gene linkage studies were able to map the mutation to chromosome 7. Chromosome walking and jumping techniques were then used to identify and sequence the gene.[62]

CF is also widely known in the United States as "65 Roses." The phrase came into being when it was used by a young boy who had overheard his mother speaking of his illness. He later informed her that he knew she was working to help with "sixty-five roses"[63] The term has since been used as a symbol by organizations and families of cystic fibrosis victims.


See also



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