|Year : 2017 | Volume
| Issue : 2 | Page : 105-112
Geographical distribution of cystic fibrosis; The past 70 years of data analyzis
Seyed Bashir Mirtajani1, Poopak Farnia2, Maryam Hassanzad3, Jalaledin Ghanavi1, Parissa Farnia1, Ali Akbar Velayati1
1 Mycobacteriology Research Center (MRC), National Research Institute of Tuberculosis and Lung Disease (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
2 Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
3 Paediatric Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
|Date of Web Publication||23-Nov-2017|
Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran
Source of Support: None, Conflict of Interest: None
Cystic fibrosis (CF) has been generally well defined throughout the world although its prevalence is very difficult to ascertain for a number of reasons, including the fact that the medical/scientific literature and patient registries vary in quality in different countries. In the present review literature (1938–2017), we found out the higher frequency of registered CF patients in the European Union. This could be due to strong clinical awareness and greater health facilities. In contrast, we found a very irregular report from Asian and African countries. In these countries, the national CF registration system is mostly lacking or it is individualized-based research. In this situation, the estimation of various risk factors such as ethnicity and/or races is remained to be resolved. Overall, this review outlines the urgent need for revitalization of national and global CF registration, worldwide.
Keywords: Cystic fibrosis, ethnicity, geographical distribution
|How to cite this article:|
Mirtajani SB, Farnia P, Hassanzad M, Ghanavi J, Farnia P, Velayati AA. Geographical distribution of cystic fibrosis; The past 70 years of data analyzis. Biomed Biotechnol Res J 2017;1:105-12
|How to cite this URL:|
Mirtajani SB, Farnia P, Hassanzad M, Ghanavi J, Farnia P, Velayati AA. Geographical distribution of cystic fibrosis; The past 70 years of data analyzis. Biomed Biotechnol Res J [serial online] 2017 [cited 2019 Jul 22];1:105-12. Available from: http://www.bmbtrj.org/text.asp?2017/1/2/105/219112
| Introduction|| |
Cystic fibrosis (CF) is an autosomal genetic disease (i.e., not sex linked) that causes an accumulation of mucus in exocrine- and exocrine-associated organs.,, The main symptoms include a persistent cough that produces mucous, recurrent lung infection, intestinal obstruction, malabsorption, nasal polyps, rectal prolapse, pancreatitis, increase of blood sugar level, and growth hormones disorders [Figure 1]., Therefore, the main effected organs in CF diseases are respiratory, digestive, and reproductive tracts. Lungs in CF diseases lose their ability to maintain a sterile surface. That is, these organs will be damaged by bacterial infections gradually. The amount of intestinal fluid is lower than normal; hence, after a dehydration of the stool, patient will suffer from bowel obstruction. The pancreatic duct also secretes less fluid than normal, causing ductal blockage and eventually pancreatic degeneration. As a result, loss of pancreatic enzymes causes steatorrhea that may offset the tendency for intestinal block. Generally, CF is mainly appeared in infants and childhood. The bases of CF are the mutation that occurs in CFtransmembrane conductance regulator (CFTR) gene., The CFTR gene is located on chromosome 7q31.2 and consists of 27 exons. This gene produces CFTR protein, a member of the ATP Binding Cassette family. CFTR protein presents on epithelial cells of many organs including the lung, liver, pancreas, digestive tract, and reproductive tract. Normally, CFTR protein controls the flow of chloride and thiocyanate ions across the epithelial cells. Indeed, ions freely flow in and out of the cells while CFTR works properly. However, if CFTR does not work correctly, ions cannot cross the membrane. As a result, thickened mucous is formed in the lung, pancreas, and other organs. This sticky mucus obstructs the airways and glands. In addition, it causes the bacterial trapping. So far, several mutations in CFTR genes have been reported, of which mutations in ΔF508, N1303K, G542X, 1717-1G>A, R553X, W1282X, G551D, 621 + 1G > T, ΔI507, and R560 had gained more clinical attention.,, The most frequent mutation is identified as ΔF508. This mutation acts by eliminating phenylalanine at position F508. Thus, the protein would not fold normally and is more quickly would be degraded. The extent and complication of CF are due to polymorphisms in CFTR gene. In fact, it is highly variable in different populations. In the present investigation, we tried to review the incidence of reported CF cases in different continents of the world.
|Figure 1: Signs and common disorders of the disease cystic fibrosis. These symptoms are different in different patients, and patients with one or more different emblem refer|
Click here to view
There is no exact document showing when the first clinical case of CF was identified. References have been found in medical texts as early as 1595 which linked salty skin and damage of the pancreas with death in childhood by infants who were “hexed” or “bewitched.” In this regard, Pieter Pauw (1564-1617) performed the first autopsy of an 11-year old female child in the anatomical theater in Leiden. He showed that the death was due to oddly swollen pancreas. Thereafter, in 1606, Alonso y de los Ruyzes de Fonteca, Professor of Medicine at Henares in Spain, described the salty taste of infants with CF. In the mid-sixteenth century, steatorrhea was recognized as an indicator of CF., Moreover, Samuel Gee in 1888 reported digestive tract problems in CF patients, i.e., arrest of growth, a distended abdomen, and attacks of diarrhea with large, pale, foul-smelling stools. These symptoms were as a result of the injury and clear change of pancreatic function. Furthermore, Landsteiner (1905), who also has defined blood groups, published the report on association of meconium ileus with defective CF pancreas. Later on, from 1930 to 1940, many findings were obtained about CF. Indeed, the terminology of CF began to develop during the 1930s. During these years, the descriptions focused on pancreatic disorders, steatorrhea, and bronchopulmonary complications. Of this, Fanconi et al. in 1936 referred the diseases as cystic fibrosis with bronchiectasis and have separated it from celiac disease. Besides, in other work by Anderson in 1938, the term “CF of the pancreas” was used. Further, in 1945, Farber had introduced the term “mucoviscidosis” (state of thickened mucus that causes the diseases) instead of what Anderson has proposed. This term still is in use in non-speaking English countries. As a matter of fact, first researchers who provided compelling evidence about source of CF were Andersen and Hodges in 1946. They reported CF as a genetic disorder as well as stems in an autosomal recessive mutation. In the next 6 years, Sant' Agnese from Columbia discovered the dissolution of salt (sodium chloride) as a disease index in patients with CF. Quickly, the sweat test became a most reliable diagnostic test to identify patients with CF. However, to clarify the clearest criteria, both pathological demonstrations such as (abnormal thick or sticky mucus or proteinaceous in the lumens of pancreas, lung, and intestine) and abnormal salty secretions of sweet glands are required. Further research revealed the differences in age and gender in CF. Generally, the incidence of this disease in children is higher than in adults. According to the published studies in European countries, there are approximately four CF children for every three CF adults. A study by McCormick et al. (2010) showed that 53% of patients were under 18 years of age and only 5% of CF patients could survive over 40 of age. Although, in Asian countries, CF children are between 1 and 5 years of ages, majority of them expired within first 5 years of their live., Besides the age, the gender was reported in correlation with CF development and survival. For instance, in an investigation conducted in Europe, the ratio of men with CF was 1.1 folds more than women. This means that about 53% of the reported patients in Europe were male. These results are widely acknowledged by other researchers. On the other hand, according to a study published in 1985 by Sturgess et al., the CF development in Canadian men was 53.57% of the total population. In this regard, Dodge et al. reported the survival rate of 55% for CF male patients and 49% for CF female patients. Moreover, the patient's data reported as 91% in 1988 and 88% in 1992. Furthermore, in 1997, it was 96%. The estimated CF population in mid-year of 2003 was 8284. As shown in the previous studies, most of reported CF patients are children, and the frequency of infection in male is 6%–8% higher than female subjects [Figure 2] and [Figure 3].,,,, To summarize and analyze various evidence-based research on CF, different public health organization tried to launch a national level of CF registry. Among these organizations, CF Foundation in the United Stated of America (USA) (1955); Canadian CF Foundation (1959), United kingdom of CF Trust (1964), and Vaincre la Mucoviscidose (1964) can be named. Subsequent to these countries, many more CF foundation has established worldwide. Finally, the International Organization for CF was formed in 1964 in Paris. Through this organization, various research activities including pathological, molecular, treatment protocols and epidemiological investigations in relation with CF were established.
|Figure 2: Distribution of patients with age-related cystic fibrosis in the UK over 56 years (1947–2003)|
Click here to view
|Figure 3: The proportion of patients with cystic fibrosis based on the gender of patients|
Click here to view
| Methods|| |
Literature search strategy
This manuscript is a review of previous published studies in various continents during 1938–2017. All articles used in this study were collected from Scopus, PubMed, Google Scholar, and ScienceDirect using the keywords of “cystic fibrosis,” “distribution of CF,” and “Epidemiology of CF.”
Inclusion and exclusion criteria
The subjects of used articles were about distribution, epidemiology, genetics, and pathology of patients with CF. In total, 341 articles used for evaluation; 92 articles (review, original and case report articles and books) were selected.
Epidemiology of cystic fibrosis
Today, clinical epidemiology means an investigation that shows the incidence of disease in human populations. Practically, epidemiological studies reveal measurable parameters for understanding the root and pattern of transmission within specific communities. This ability will help policymakers to design general policies about the disease. During recent years, many investigators had focused on frequency and/or prevalence of CF., Previous studies showed variable prevalence of CF among different races [Figure 4]. In addition, Hill et al. (1998) suggested the frequent incidence of CF among Whites. Later on, this observation was confirmed by Westwood et al. in 2007. In another multicenter study that conducted in 27 European countries, the CF incidence was rated as 0.073% of total population. A variety of risk factors such as racial purity, the immigration, racial integration, mutation, and sometimes environmental factors can be considered as disease development.,, However, distribution of risk factors can be variable in different population.,, Thereby, in the present study, the various risk factors in different continent were highlighted separately.
|Figure 4: The above picture shows the difference in the distribution of outbreaks in different continents. Accordingly, the highest rates in Europe and lowest is in East Asia|
Click here to view
The statistical analysis of the various continents regarding prevalence of CF showed that Asia has the lowest rate of patients with the disease [Figure 5]. According to data from the World Health Organization (WHO), there is no detailed information on the prevalence of CF in Asia. Although this can be due to lack of registration, we know that many Asian countries do not have the national CF registration. Furthermore, available data have gathered from case series studies or individualized hospital reports. Based on what is available, the number of reported CF patients in West Asia is one in every 4000–10,000 people, while the number in East Asia is much lower, i.e., one case in every 100,000–350,000., For instance, in India as a country in West Asia, the prevalence of CF is one case per 43,321–100,323 people. In addition, the statistics in Japan is (in the East) one case per 350,000 people. Among other Asian countries, the Middle-Eastern ones have very limited information [Figure 6].,,,, This is again can be due to lack of National CF Registry and/or improper reporting system. In addition, lack of medical awareness as well as premature deaths as results of undiagnosed treatment is worsening the situation. Based on average statistical analysis in the Middle East, one in every 2560 to 15,876 cases was developed CF [Figure 4]. The incidence is variable among different regions, e.g., one patients reported in Bahrain within the last 15 years. In contrast, 11 CF infants reported in 1 year in Lebanon., The reported rate for Iran was 1 in 100,000. In addition, research studies revealed a mutation at F508del in CFTR gene in the majority of CF patients. In this regard, the frequency of mutation at F508del in CFTR gene was 37.5%; 24%, and 18%–23% in Lebanon, Turkey, and Iran, respectively.,,,,,, Investigators suggested that inter-familial marriage in these regions is a crucial risk factor for CF development.
|Figure 5: The incidence of cystic fibrosis on the map according to the World Health Organization|
Click here to view
|Figure 6: The distribution of patients with cystic fibrosis in a number of countries in the Middle East. According to the above-mentioned data, lack of uniform distribution is visible|
Click here to view
The first report of CF refers to 1959 in a South African newborn. This child died shortly after birth due to meconium ileus. In addition, during the next 3 years, different cases were reported in various regions of the African continent., However, due to geographical and geopolitical situation, the in-depth investigation remains obscure., In addition, few studies demonstrated importance of mutation in the gene CFTR (3120 + 1G → A) among African nations. The Official WHO statistics show a 70%–79% mutation outbreak in the CFTR genes, in Tunisia and Algeria. According to a study published in (1999), the prevalence of CF among African population in the south region was higher than people living in the East and West of Africa. Indeed during 1998–2000, no cases of CF were reported from the western region of Africa. Possibly, through this period, most of health care authorities were involved in deceasing malnutrition, poverty, and/or controlling the deadly spread of tuberculosis and HIV infection.,
Frequency of CF in North America is 1 out of every 2500 people. However, there are differences in its distribution across the American continent. The prevalence of CF in the US Whites is 1 in every 2900 babies. In Canada, the data are 1 in every 2500 babies [Figure 7].,,, This can be due to differences of ethnicity or races in North America. The White races are higher than other races, i. e., Native Americans, Hispanics, and Blacks,, and since White races have higher racial purity, they might be more prone to develop CF, which needs further investigation.
|Figure 7: Distribution of cystic fibrosis patients in North America. According to Figure 5, cystic fibrosis prevalence rate in Whites, more than any other American races|
Click here to view
South America as a continent with enormous racial disparity has a high distribution of CF patients. Outbreaks on the continent were depending on regions and countries of residence between 1 case in 3500 and 8500 people., [Table 1] shows the distribution of CF patients in four countries of Latin America. Accordingly, the distribution of CF in the northern region (Mexico), South (Argentina), then to the East (Brazil), and West (Chile) shows a higher number. In the meantime, it shows the highest level of contamination in Southern Argentina. Adverse economic conditions such as high mortality due to disease, lack of proper diagnosis, and management of respiratory infections are factors which affecting the figures on the distribution of this disease.
|Table 1: People with cystic fibrosis in Latin America, between 1968 and 1989|
Click here to view
In comparison with other continents, Europe is reported to have the highest level of CF. The high prevalence of CF in Europe has caused countries in the continent to carry out severe screening programs for this disease., Existing programs such as nail-patella syndrome for genetic disease screening helped to make this decision. With the establishment of the European CF Society (ECFS) in 2004, the process has been speeding up. The high level can be as a result of proper registry and strong clinical awareness. In Europe, there is a very well organized registration system which maintained by the ECFS. Acquired data from both national CF registries and individual CF centers would enter to the systems on regular bases throughout Europe., Therefore, the picture of CF is very clear cut in Europe [Figure 8].
|Figure 8: The number of dead people with cystic fibrosis in Europe (divided year and country)|
Click here to view
As shown in [Table 2], the distribution of CF is more dramatic in northern, northwestern, and central Europe. Indeed, Farrell et al. in 2007 reported the highest birth rate of CF (1 in 1353 people) in Ireland. However, Germany with 82/425 patients had the highest number of patients., Among countries located in the northern region of Europe, the Finland showed the lowest rate of CF disease (1 in 25000 people)., On the other hand, other parts of Europe are all homogeneous in this regard approximately., This is probably stems in proximity between the races, and the racial mixing. In fact, studies showed that F508del mutation in gene CFTR is more frequent (70%) among European patients among European patients.
|Table 2: Distribution to cystic fibrosis patients in the countries of Europe|
Click here to view
As racial differences in Australia, the incidence and distribution of CF patients are variable [Figure 9].,,, The highest prevalence in Australia is related to the Britain immigrants, with 1 case in every 2021 birth. Although for other races the rate is decreased by 2.5 folds.
|Figure 9: Distribution of cystic fibrosis patients in Australia and New Zealand|
Click here to view
| Conclusion|| |
As shown, a considerable number of countries, especially those located in Africa, parts of Asia, and parts of the South America, have no or limited registration system. It is understandable that health authorities in these countries have no choice but ignoring CF that is due to other important and priorities in public issues, for instance, civil war, poverty, malnutrition, and outbreaks of infectious diseases such as tuberculosis. The policy in these regions needs to be reviewed. According to the collected information, it is realistic to acclaim that more than 50% of countries in different continents have no information. This situation has already been discussed in global policy. As a consequence, the WHO has already listed the CF as important disease and asked all countries to update their data and reports on CF cases. This will ultimately make the countries to plan for National Registry of CF. Hopefully, within the next few years, the global distribution of diseases and other strategically plans become possible.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Ahn KM, Park HY, Lee JH, Lee MG, Kim JH, Kang IJ, et al.
Cystic fibrosis in Korean children: A case report identified by a quantitative pilocarpine iontophoresis sweat test and genetic analysis. J Korean Med Sci 2005;20:153-7.
Riordan JR, Rommens JM, Kerem B, Alon N, Rozmahel R, Grzelczak Z, et al.
Identification of the cystic fibrosis gene: Cloning and characterization of complementary DNA. Science 1989;245:1066-73.
Donaldson SH, Bennett WD, Zeman KL, Knowles MR, Tarran R, Boucher RC, et al.
Mucus clearance and lung function in cystic fibrosis with hypertonic saline. N Engl J Med 2006;354:241-50.
Khorrami A, Bonyadi M, Rafeey M, Omrani O. Association of TNF-α gene variants with clinical manifestation of cystic fibrosis patients of Iranian Azeri Turkish ethnicity. Iran J Pediatr 2015;25:e307.
Smith JJ, Travis SM, Greenberg EP, Welsh MJ. Cystic fibrosis airway epithelia fail to kill bacteria because of abnormal airway surface fluid. Cell 1996;85:229-36.
Colombo C, Ellemunter H, Houwen R, Munck A, Taylor C, Wilschanski M, et al.
Guidelines for the diagnosis and management of distal intestinal obstruction syndrome in cystic fibrosis patients. J Cyst Fibros 2011;10 Suppl 2:S24-8.
Durno C, Corey M, Zielenski J, Tullis E, Tsui LC, Durie P, et al.
Genotype and phenotype correlations in patients with cystic fibrosis and pancreatitis. Gastroenterology 2002;123:1857-64.
Ratjen F, Bell SC, Rowe SM, Goss CH, Quittner AL, Bush A. Cystic fi brosis. Nat Rev Dis Primers 2015; 1:1
Kammesheidt A, Kharrazi M, Graham S, Young S, Pearl M, Dunlop C, et al.
Comprehensive genetic analysis of the cystic fibrosis transmembrane conductance regulator from dried blood specimens – Implications for newborn screening. Genet Med 2006;8:557-62.
Cozens AL, Yezzi MJ, Kunzelmann K, Ohrui T, Chin L, Eng K, et al.
CFTR expression and chloride secretion in polarized immortal human bronchial epithelial cells. Am J Respir Cell Mol Biol 1994;10:38-47.
Koch C, Høiby N. Pathogenesis of cystic fibrosis. Lancet 1993;341:1065-9.
Bonyadi M, Omrani O, Rafeey M, Bilan N. Spectrum of CFTR gene mutations in Iranian Azeri Turkish patients with cystic fibrosis. Genet Test Mol Biomarkers 2011;15:89-92.
Population variation of common cystic fibrosis mutations. The Cystic Fibrosis Genetic Analysis Consortium. Hum Mutat 1994;4:167-77.
Tsui LC. The spectrum of cystic fibrosis mutations. Trends Genet 1992;8:392-8.
Kerem E, Corey M, Kerem BS, Rommens J, Markiewicz D, Levison H, et al
. The relation between genotype and phenotype in cystic fibrosis-analysis of the most common mutation (ΔF508). N Engl J Med 1990;323:1517-22.
Spoonhower KA, Davis PB. Epidemiology of cystic fibrosis. Clin Chest Med 2016;37:1-8.
Busch R. On the history of cystic fibrosis. Acta Univ Carol Med (Praha) 1990;36:13-5.
Farrow NR. Cystic Fibrosis: The Role of Airway Stem Cells in Sustained Gene Expression by Lentiviral Directed Gene Therapy; 2015.
Busch R. To the early history of cystic pancreatic fibromatosis (On the beginnings of the history of cystic fibroma of the pancreas). NTM Series of Books for the History of Science and Technology. Vol. 16. Leipzig; 1979. p. 95-107.
Home E. On the formation of fat in the intestines of living animals. Proc R Soc Lond I1800;1:462-3.
Bush AG, Duncan M, Hodson ME. Cystic Fibrosis. 3rd
ed. London: Hodder Arnold; 2007. p. 503-22.
Landsteiner K. Meconium ileus by Eingedticktes pancreatitis. Zentralbl Allg Pathol 1905;16:903-7.
Andersen DH. Cystic fibrosis of the pancreas and its relation to celiac disease: A clinical and pathologic study. Am J Dis Child 1938;56:344-99.
Morrissey SM, Tymvios MC. Acid mucins in human intestinal goblet cells. J Pathol 1978;126:197-208.
Andersen DH, Hodges RG. Celiac syndrome; genetics of cystic fibrosis of the pancreas, with a consideration of etiology. Am J Dis Child 1946;72:62-80.
Barbero GJ, Sibinga MS. Enlargement of the submaxillary salivary glands in cystic fibrosis. Pediatrics 1962;29:788-93.
di Sant'agnese PA, Davis PB. Cystic fibrosis in adults 75 cases and a review of 232 cases in the literature. Am J Med 1979;66:121-32.
Mehta G, Macek M Jr., Mehta A; European Registry Working Group. Cystic fibrosis across Europe: EuroCareCF analysis of demographic data from 35 countries. J Cyst Fibros 2010;9 Suppl 2:S5-21.
Modaresi M, Faghihinia J, Baharzadeh F. Cystic fibrosis prevalence among a group of high-risk Iranian children. J Isfahan Med Sch 2012;30: 1-7.
Powers CA, Potter EM, Wessel HU, Lloyd-Still JD. Cystic fibrosis in Asian Indians. Arch Pediatr Adolesc Med 1996;150:554-5.
FitzSimmons SC. The changing epidemiology of cystic fibrosis. J Pediatr 1993;122:1-9.
Sturgess JM, Czegledy-Nagy E, Corey M, Thompson MW. Cystic fibrosis in Ontario. Am J Med Genet 1985;22:383-93.
Dodge JA, Lewis PA, Stanton M, Wilsher J. Cystic fibrosis mortality and survival in the UK: 1947-2003. Eur Respir J 2007;29:522-6.
Fletcher RH, Fletcher SW, Fletcher GS. Clinical Epidemiology: The Essentials. Wolters Kluwer Health: Lippincott Williams & Wilkins; 2012.
Shaikh BT, Hatcher J. Health seeking behaviour and health service utilization in Pakistan: Challenging the policy makers. J Public Health (Oxf) 2005;27:49-54.
Kelly J. Environmental scan of cystic fibrosis research worldwide. J Cyst Fibros 2017;16:367-70.
Westwood T. The epidemiology of cystic fibrosis in the Western Cape Province. South Afr J Child Health 2007;1:78-81.
Farrell PM. The prevalence of cystic fibrosis in the European Union. J Cyst Fibros 2008;7:450-3.
World Health Organization. The Molecular Genetic Epidemiology of Cystic Fibrosis. Report of a Joint Meeting of WHO/ECFTN/ICF (M) A/ECFS. Geneva: WHO; 2004.
Pianka ER. Latitudinal gradients in species diversity: A review of concepts. Am Nat 1966;100:33-46.
Currie DJ. Energy and large-scale patterns of animal-and plant-species richness. Am Nat 1991;137:27-49.
Rohde K. Latitudinal gradients in species diversity and Rapoport's rule revisited: A review of recent work and what can parasites teach us about the causes of the gradients? Ecography 1999;22:593-613.
O'Sullivan BP, Freedman SD. Cystic fibrosis. Lancet 2009;373:1891-904.
Cuppens H, Boulyjenkov V, Cassiman J, Cutting G, Dodge J, Des Georges M, et al
. The Molecular Genetic Epidemiology of Cystic Fibrosis: Report of a Joint Meeting of WHO/ECFTN/ICF (M) A/ECFS; 2004.
Singh M, Rebordosa C, Bernholz J, Sharma N. Epidemiology and genetics of cystic fibrosis in Asia: In preparation for the next-generation treatments. Respirology 2015;20:1172-81.
Desgeorges M, Mégarbané A, Guittard C, Carles S, Loiselet J, Demaille J, et al.
Cystic fibrosis in lebanon: Distribution of CFTR mutations among Arab communities. Hum Genet 1997;100:279-83.
Al-Mahroos F. Cystic fibrosis in bahrain incidence, phenotype, and outcome. J Trop Pediatr 1998;44:35-9.
Havasian MR, Panahi J, Mahdieh N. Cystic fibrosis and distribution and mutation analysis of CFTR gene in Iranian patients. Koomesh 2014;15: 431-40.
Kollberg H. Cystic fibrosis in Kuwait. J Trop Pediatr 1986;32:293-4.
Alibakhshi R, Zamani M. Mutation analysis of CFTR gene in 70 Iranian cystic fibrosis patients. Iran J Allergy Asthma Immunol 2006;5:3-8.
Bobadilla JL, Macek M Jr., Fine JP, Farrell PM. Cystic fibrosis: A worldwide analysis of CFTR mutations – correlation with incidence data and application to screening. Hum Mutat 2002;19:575-606.
Guilloud-Bataille M, De Crozes D, Rault G, Degioanni A, Feingold J. Cystic fibrosis mutations: Report from the French registry. The clinical centers of the CF. Hum Hered 2000;50:142-5.
Wald NJ, Morris JK, Rodeck CH, Haddow JE, Palomaki GE. Cystic fibrosis: Selecting the prenatal screening strategy of choice. Prenat Diagn 2003;23:474-83.
Teder M, Klaassen T, Oitmaa E, Kaasik K, Metspalu A. Distribution of CFTR gene mutations in cystic fibrosis patients from estonia. J Med Genet 2000;37:E16.
Kholghi Oskooei V, Esmaeili Dooki MR, Tabaripour R, Mirzajani S, Pourbagher R, Akhavan-Niaki H, et al.
CFTR haplotypes in Northern Iranian population. Gene 2013;512:55-60.
Padoa C, Goldman A, Jenkins T, Ramsay M. Cystic fibrosis carrier frequencies in populations of African origin. J Med Genet 1999;36:41-4.
Carles S, Desgeorges M, Goldman A, Thiart R, Guittard C, Kitazos CA, et al.
First report of CFTR mutations in black cystic fibrosis patients of Southern African origin. J Med Genet 1996;33:802-4.
Levin SE, Blumberg H, Zamit R, Schmaman A, Wagstaff L. Mucoviscidosis (cystic fibrosis of the pancreas) in bantu twin neonates. S Afr Med J 1967;41:482-5.
Velayati AA, Bakayev V, Bahadori M, Tabatabaei SJ, Alaei A, Farahbood A, et al.
Religious and cultural traits in HIV/AIDS epidemics in Sub-Saharan Africa. Arch Iran Med 2007;10:486-97.
Coovadia H, Jewkes R, Barron P, Sanders D, McIntyre D. The health and health system of South Africa: Historical roots of current public health challenges. Lancet 2009;374:817-34.
Kosorok MR, Wei WH, Farrell PM. The incidence of cystic fibrosis. Stat Med 1996;15:449-62.
Dupuis A, Hamilton D, Cole DE, Corey M. Cystic fibrosis birth rates in Canada: A decreasing trend since the onset of genetic testing. J Pediatr 2005;147:312-5.
Corey M, Farewell V. Determinants of mortality from cystic fibrosis in Canada, 1970-1989. Am J Epidemiol 1996;143:1007-17.
Grosse SD, Boyle CA, Botkin JR, Comeau AM, Kharrazi M, Rosenfeld M, et al.
Newborn screening for cystic fibrosis: Evaluation of benefits and risks and recommendations for state newborn screening programs. MMWR Recomm Rep 2004;53:1-36.
Collazo T, Magarino C, Chavez R, Suardiaz B, Gispert S, Gomez M, et al.
Frequency of delta-F508 mutation and XV2C/KM19 haplotypes in cuban cystic fibrosis families. Hum Hered 1995;45:55-7.
Orozco L, Velázquez R, Zielenski J, Tsui LC, Chávez M, Lezana JL, et al.
Spectrum of CFTR mutations in Mexican cystic fibrosis patients: Identification of five novel mutations (W1098C, 846delT, P750L, 4160insGGGG and 297-1G- and gt; A). Hum Genet 2000;106:360-5.
Macri CN, de Gentile AS, Manterola A, Tomezzoli S, Reis FC, Largo Garcia I, et al.
Epidemiology of cystic fibrosis in latin America: Preliminary communication. Pediatr Pulmonol 1991;10:249-53.
Shwachman H. Therapy of cystic fibrosis of the pancreas. Pediatrics 1960;25:155-63.
Barben J, Castellani C, Dankert-Roelse J, Gartner S, Kashirskaya N, Linnane B, et al.
The expansion and performance of national newborn screening programmes for cystic fibrosis in Europe. J Cyst Fibros 2017;16:207-13.
Burgard P, Rupp K, Lindner M, Haege G, Rigter T, Weinreich SS, et al.
Newborn screening programmes in Europe; arguments and efforts regarding harmonization. Part 2. From screening laboratory results to treatment, follow-up and quality assurance. J Inherit Metab Dis 2012;35:613-25.
Castellani C, Massie J, Sontag M, Southern KW. Newborn screening for cystic fibrosis. Lancet Respir Med 2016;4:653-61.
Southern KW, Munck A, Pollitt R, Travert G, Zanolla L, Dankert-Roelse J, et al.
A survey of newborn screening for cystic fibrosis in Europe. J Cyst Fibros 2007;6:57-65.
Castellani C, Southern KW, Brownlee K, Dankert Roelse J, Duff A, Farrell M, et al.
European best practice guidelines for cystic fibrosis neonatal screening. J Cyst Fibros 2009;8:153-73.
Kerem E, Conway S, Elborn S, Heijerman H, Consensus Committee. Standards of care for patients with cystic fibrosis: A European consensus. J Cyst Fibros 2005;4:7-26.
Klaassen T, Teder M, Viikmaa M, Metspalu A. Neonatal screening for the cystic fibrosis main mutation delta F508 in Estonia. J Med Screen 1998;5:16-9.
Romeo G, Devoto M, Galietta LJ. Why is the cystic fibrosis gene so frequent? Hum Genet 1989;84:1-5.
Schulz S, Jakubiczka S, Kropf S, Nickel I, Muschke P, Kleinstein J, et al.
Increased frequency of cystic fibrosis transmembrane conductance regulator gene mutations in infertile males. Fertil Steril 2006;85:135-8.
Nielsen R, Gyrd-Hansen D. Prenatal screening for cystic fibrosis: An economic analysis. Health Econ 2002;11:285-99.
Kere J, Estivill X, Chillón M, Morral N, Nunes V, Norio R, et al.
Cystic fibrosis in a low-incidence population: Two major mutations in Finland. Hum Genet 1994;93:162-6.
Slieker MG, Uiterwaal CS, Sinaasappel M, Heijerman HG, van der Laag J, van der Ent CK, et al.
Birth prevalence and survival in cystic fibrosis: A national cohort study in the Netherlands. Chest 2005;128:2309-15.
Claustres M, Guittard C, Bozon D, Chevalier F, Verlingue C, Ferec C, et al.
Spectrum of CFTR mutations in cystic fibrosis and in congenital absence of the vas deferens in France. Hum Mutat 2000;16:143-56.
Goldhaber-Fiebert JD, Brandeau ML. Evaluating cost-effectiveness of interventions that affect fertility and childbearing: How health effects are measured matters. Med Decis Making 2015;35:818-46.
Allan JL, Phelan PD. Incidence of cystic fibrosis in ethnic italians and greeks and in australians of predominantly British origin. Acta Paediatr Scand 1985;74:286-9.
Massie RJ, Olsen M, Glazner J, Robertson CF, Francis I. Newborn screening for cystic fibrosis in victoria: 10 years' experience (1989-1998). Med J Aust 2000;172:584-7.
Robinson PG, Elliott RB, Fraser J. Cystic fibrosis in New Zealand: Incidence and mortality data. N Z Med J 1976;83:268-70.
Wesley AW, Stewart AW. Cystic fibrosis in New Zealand: Incidence and mortality. N Z Med J 1985;98:321-3.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9]
[Table 1], [Table 2]