Cystic fibrosis: A worldwide analysis of CFTR mutations—correlation with incidence data and application to screening
Version of Record online: 3 MAY 2002
Copyright © 2002 Wiley-Liss, Inc.
Volume 19, Issue 6, pages 575–606, June 2002
How to Cite
Bobadilla, J. L., Macek, M., Fine, J. P. and Farrell, P. M. (2002), Cystic fibrosis: A worldwide analysis of CFTR mutations—correlation with incidence data and application to screening. Hum. Mutat., 19: 575–606. doi: 10.1002/humu.10041
- Issue online: 3 MAY 2002
- Version of Record online: 3 MAY 2002
- Manuscript Accepted: 1 MAR 2002
- Manuscript Received: 19 JUN 2001
- National Center for Research Resources to the University of Wisconsin Medical School
- Academic Generalist Scholarship Program from the American College of Physicians-American Society of Internal Medicine, Wisconsin Chapter
- National Institutes of Health. Grant Numbers: DK 34108, M01 RR03186
- Internal Grant Agency of the Czech Ministry of Health (IGA MZ CR). Grant Numbers: 6250-3, 6464-3, 00000064203
- Ministry of Education of the Czech Republic. Grant Numbers: 111300003, LN 00A079, ME451
- 1996. Newborn screening. Adv Pediatr 43:231–270. .
- 1997. Cystic fibrosis mutations and associated haplotypes in Bulgaria—a comparative population genetic study. Hum Genet 99:513–520. .
- 1999. Geographic distribution of cystic fibrosis transmembrane regulator gene mutations in Saudi Arabia. Ann Trop Paediatr 19:69–73. .
- 1996. Frequencies of cystic fibrosis mutations in the Maine population: high proportion of unknown alleles in individuals of French-Canadian ancestry. Hum Genet 98:207–209. .
- 2000. Molecular analysis in Brazilian cystic fibrosis patients reveals five novel mutations. Genet Test 4:69–74. .
- 1995. Analysis of the complete coding region of the CFTR gene in a cohort of CF patients from North-East Italy: identification of 90% of the mutations. Hum Genet 95:397–402. .
- 1999. Cystic fibrosis: low frequency of DF508 mutation in 2 population samples from Rio de Janeiro, Brazil. Hum Biol 71:189–196. .
- 2001. The 3120+1GA splicing mutation in CFTR is common in Brazilian cystic fibrosis patients. Hum Biology 73:403–409. .
- 1996. First report of CFTR mutations in black cystic fibrosis patients of southern African origin. J Med Genet 33:802–804. .
- 1996. Detection of more than 91% cystic fibrosis mutations in a sample of the population from Reunion Island and identification of two novel mutations (A309G, S1255L) and one novel polymorphism (L49L). Clin Genet 54:437–439. .
- 1993. Cystic fibrosis in Spain: high frequency of mutation G542X in the Mediterranean coastal area. Hum Genet 91:66–70. .
- 1997. High heterogeneity for cystic fibrosis in Spanish families: 75 mutations account for 90% of chromosomes. Hum Genet 101:365–370. .
- 1995. Identical intragenic microsatellite haplotype found in cystic fibrosis chromosomes bearing mutation G551D in Irish, English, Scottish, Breton and Czech patients. Hum Hered 45:6–12. .
- 1996. Molecular epidemiology of cystic fibrosis mutations and haplotype in southern Italy evaluated with an improved semiautomatic robotic procedure. J Med Genet 33:475–479. .
- 1999. Detection of five rare cystic fibrosis mutations peculiar to Southern Italy: implications in screening for the disease and phenotype characterization for patients with homozygote mutations. Clin Chem 45:957–962. .
- 1993. Direct sequencing of the complete CFTR gene: the molecular characterization of 99. 5% of CF chromosomes in Wales. Hum Molec Genet 2:1551–1556. .
- 1997. Spectrum of CFTR mutations in Argentine cystic fibrosis patients. Clin Genet 51:43–47. .
- 1994. Mutation analysis in 600 French cystic fibrosis patients. J Med Genet 31:541–544. .
- 1994. Analysis of the CFTR gene confirms the high genetic heterogeneity of the Spanish population: 43 mutation account for only 78% of CF chromosomes. Hum Genet 93:447–451. .
- 1993. Analysis of the 27 exons and flanking regions of the cystic fibrosis gene: 40 different mutations account for 91. 2% of the mutant alleles in Southern France. Hum Molec Genet 2:1209–1213. .
- 2000. Spectrum of CFTR mutations in cystic fibrosis and in congenital absence of the vas deferens in France. Hum Mutat 16:143–156. .
- 1998. Relative frequencies of cystic fibrosis mutations in The Netherlands as an illustration of significant regional variation in a small country. Hum Genet 102:587–590. .
- 1993. Detection of 98. 5% of the mutations in 200 Belgian cystic fibrosis alleles by reverse dot-blot and sequencing of the complete coding region and exon/intron junctions of the CFTR gene. Genomics 18:693–697. .
- Cystic Fibrosis Foundation. 1998. Patient registry, 1997: annual data report. Bethesda MD: Cystic Fibrosis Foundation. p. 3.
- Cystic Fibrosis Genetic Analysis Consortium (CFGAC). 1994. Population variation of common cystic fibrosis mutations. Hum Mutat 4:167–177.
- Cystic Fibrosis Genetic Analysis Consortium (CFGAC). 2000.www.genet.sickkids.on.ca/cftr/.
- 1992. Frequency of the ΔF508 deletion and G551D, R553X and G542X mutations in Yugoslav CF patients. Hum Genet 88:699–700. .
- 1998. Complete identification of cystic fibrosis transmembrane conductance regulator mutations in the CF population of Saguenay Lac-Saint-Jean (Quebec, Canada). Clin Genet 53:44–46. .
- 1997. Cystic fibrosis in Lebanon: distribution of CFTR mutations among Arab communities. Hum Genet 100:279–283. .
- 1992. A termination mutation (2143delT) in the CFTR gene of German cystic fibrosis patients. Hum Genet 90:279–284. .
- 1994. Detection of more than 50 different CFTR mutations in a large group of German cystic fibrosis patients. Hum Genet 94:542–553. .
- 1998. Evidence for a common ethnic origin of cystic fibrosis mutation 3120+1GA in diverse populations. Am J Hum Genet 63:656–662. .
- 2000. Characterization of a novel 21kb deletion, CFTRdele2,3(21 kb), in the CFTR gene a cystic fibrosis mutation of Slavic origin common in Central and East Europe. Hum Genet 106:259–268. .
- 1997. Novel and characteristic CFTR mutations in Saudi Arab children with severe cystic fibrosis. J Med Genet 34:996–999. .
- Biomed CF Mutation Analysis Consortium. 1997. Geographic distribution and regional origin of 272 cystic fibrosis mutations in European populations. Hum Mutat 10:135–154. ,
- European Working Group on CF Genetics. 1990. Gradient of distribution in Europe of the major CF mutation and its associated haplotypes. Hum Genet 85:436–445.
- 2000. Improving the health of patients with cystic fibrosis through newborn screening. Adv Ped 49:79–115. .
- 1992. Detection of over 98% cystic fibrosis mutations in a Celtic population. Nat Genet 1:188–191. .
- 1998. Cystic fibrosis transmembrane-conductance regulator mutations among African Americans. Am J Hum Genet 62:195–196. .
- 1998. Identification of cystic fibrosis mutations in the United Arab Emirates. Hum Mutat 1:412–413. .
- 1999. Determination of the prevalence of cystic fibrosis in the United Arab Emirates by genetic carrier screening. Clin Genet 55:496–497. .
- 1995. A cystic fibrosis mutation associated with mild lung disease. NEJM 333:95–99. .
- 1999. Analysis of 31 CFTR mutations by polymerase chain reaction/oligonucleotide ligation assay in a pilot screening of 4476 newborns for cystic fibrosis. L Med Screen 3:67–69. .
- 1998. P67L: a cystic fibrosis allele with mild effects found at high frequency in the Scottish population. J Med Genet 35:122–125. .
- 2001. The molecular basis of cystic fibrosis in South Africa. Clin Genet 59:37–41. .
- 1994. Genetic analysis of Hispanic individuals with cystic fibrosis. Am J Hum Genet 54:443–446. .
- 1997. Newborn screening for cystic fibrosis in Wisconsin: comparison of biochemical and molecular methods. Pediatrics 99:819–824. .
- 2001. Laboratory standards and guidelines for population based cystic fibrosis screening. Genet Med 3:149–154. .
- The Clinical Centers of the CF French Registry. 2000. Cystic fibrosis mutations: report from the French registry. Hum Hered 50:142–145. ,
- 1991. Efficacy of statewide neonatal screening for cystic fibrosis by assay of trypsinogen concentrations. N Engl J Med 325:769–774. .
- 2001. Improved detection of cystic fibrosis mutations in the heterogeneous U.S. population using an expanded, pan-ethnic mutation panel. Genet Med 3:168–176. .
- 1997. A new mutation, 3905insT, accounts for 4. 8% of 1173 CF chromosomes in Switzerland and causes a severe phenotype. Hum Genet 100:220–223. .
- 1993. The world of the Celts. London: Thames and Hudson, Ltd. .
- 1997. Identification of novel mutations in the CFTR gene causing cystic fibrosis (CF) in Arab populations. Institut Paster del Tunis 74:93–94. .
- 1995. Mutation analysis of ten exons of the CFTR gene in Greek cystic fibrosis patients: characterization of 74. 5% of CF alleles including one novel mutation. Hum Genet 96:364–366. .
- 1994. Cystic fibrosis in a low-incidence population: two major mutations in Finland. Hum Genet 93:162–166. .
- 1989. Identification of the cystic fibrosis gene: genetic analysis. Science 245:1073–1080. .
- 1995. Highly variable incidence of cystic fibrosis and different mutation distribution among different Jewish ethnic groups in Israel. Hum Genet 96:193–197. .
- 1998. Neonatal screening for the cystic fibrosis main mutation ΔF508 in Estonia. J Med Screen 5:16–19. .
- 1996. The incidence of cystic fibrosis. Stat Med 15:449–462. .
- 1992. Genetic determination of exocrine pancreatic function in cystic fibrosis. Am J Hum Genet 50:1178–1184. .
- 1974. Cystic fibrosis in blacks in Washington, DC. AmJ Dis Child 127:64–67. .
- 1998. 3849+10kbCT splicing mutation in Hispanic CF patients. Mol Genet Metab 64:213–216. .
- 1997. G542X as a probable Phoenician cystic fibrosis mutation. Hum Biol 69:419–425. .
- 1999. Analysis of the complete coding region of the CFTR gene in ten Algerian cystic fibrosis families. Hum Hered 49:81–84. .
- 1995. Complete map of cystic fibrosis mutation DF508 frequencies in Western Europe and correlation between mutation frequencies and incidence of disease. Hum Biol 67:797–803. .
- 1991. Population study of CFTR gene mutations in Bohemia and Moravia: hypothesis on the historical spread of G551D and deltaF508 in Europe. Am J Hum Genet 49:A474, A2703. .
- 1997. Identification of common cystic fibrosis mutations in African-Americans with cystic fibrosis increases the detection rate to 75%. Am J Hum Genet 60:1122–1127. .
- 2002. Eur J Hum Genet (in press) . , et al.
- 1998. Detection of five novel mutations of the cystic fibrosis transmembrane regulator (CFTR) gene in Pakistani patients with cystic fibrosis: Y569D, Q98X, 296+12(T>C), 1161delC and 621+2(T>C). Hum Mutat 11:152–157. .
- 1992. Screening for CFTR gene mutations in a Southwest American Indian population. Am J Hum Genet 51(suppl):A340; 1341. .
- 1993. Detection of more than 94% cystic fibrosis mutations in a sample of Belgian population and identification of four novel mutations. Hum Mutat 2:16–20. .
- 1994. Complete detection of mutations in cystic fibrosis patients of Native American origin. Hum Genet 94:629–632. .
- 2001. Influence of neonatal screening and centralized treatment on long-term clinical outcome and survival of CF patients. Eur Respir J 18:306–315. .
- 1996. Distribution of CFTR mutations in cystic fibrosis patients of Tunisian origin: identification of two novel mutations. Euro J Hum Genet 4:20–24. .
- 1999. Structure and function of the cystic fibrosis transmembrane conductance regulator. Braz J Med Biol Res 32:1021–1028. .
- 1994. The origin of the major cystic fibrosis mutation (ΔF508) in European populations. Nat Genet 7:169–175. .
- 1998. Analysis of the CFTR gene in Turkish cystic fibrosis patients: identification of three novel mutations (3172delAC, P1013L and M1028I). Hum Genet 102:224–230. .
- 2001. Cystic fibrosis mutations as associated haplotypes in Turkish cystic fibrosis patients. Hum Biology 73:191–203. .
- 2001. Prevalence of cystic fibrosis mutations in Israeli jews. Genet Testing 5:47–52. .
- 1993. Frequency of ΔF508 in a Mexican sample of cystic fibrosis patients. J Med Genet 30:501–502. .
- 2000. Spectrum of CFTR mutation in Mexican cystic fibrosis patients: identification of five novel mutations (W1098C, 846delT, P750L, 4160insGGGG and 297-1GA). Hum Genet 106:360–365. .
- 1997. Molecular characterization of cystic fibrosis patients in the state of São Paulo (Brazil). J Med Genet 34:877. .
- 1999. The ΔF508 mutation in Ecuador, South America. Hum Mutat 14:348–350. .
- 1998. Molecular basis of cystic fibrosis in the Republic of Macedonia. Clin Genet 54:203–209. .
- 1997. Cystic fibrosis mutations in Romania. Eur J Pediatr 156:212–213. .
- 1999. Geographic heterogeneity of 4 common worldwide cystic fibrosis non-DF508 mutations in Brazil. Hum Biol 71:111–121. .
- 2000. CFTR mutations in three Latin American countries. Am J Med Genet 91:277–279. .
- 1989. Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science 245:1066–1072. .
- 1994. CFTR mutations in Chilean cystic fibrosis patients. Hum Genet 94:291–294. .
- 1989. Why is the cystic fibrosis gene so frequent? Hum Genet 84:1–5. .
- 1989. Identification of the cystic fibrosis gene: chromosome walking and jumping. Science 245:1059–1065. .
- 1992. Cystic fibrosis mutations in French Canadians: three CFTR mutations are relatively frequent in a Quebec population with an elevated incidence of cystic fibrosis. Am J Med Genet 42:360–364. .
- 1999. Three common CFTR mutations should be included in a neonatal screening programme for cystic fibrosis in Sweden. Clin Genet 56:318–322. .
- 1994. 394delTT: a Nordic cystic fibrosis mutation. Hum Genet 93:157–161. .
- 1995a. High incidence of cystic fibrosis on the Faroe Islands: a molecular and genealogical study. Hum Genet 95:703–706. .
- 1995b. Cystic fibrosis mutation analysis: report from 22 U.K. regional genetics laboratories. Hum Mutat 6:326–333. .
- 2000. Neonatal screening for cystic fibrosis in Brittany, France: assessment of 10 years’ experience and impact on prenatal diagnosis. Lancet 356:789–794. .
- 1990. Studies of RFLP closely linked to the cystic fibrosis locus through Europe lead to new considerations in population genetics. Hum Genet 84:449–454. .
- 1992. Association of a nonsense mutation (W1282X), the most common mutation in the Ashkenazi Jewish cystic fibrosis patients in Israel, with presentation of severe disease. Am J Hum Genet 50:222–228. .
- 1991. The incidence of different cystic fibrosis mutations in the Scottish population: effects on prenatal diagnosis and genetic counseling. J Med Genet 28:317–321. .
- 1997. Detection of 100% of the CFTR mutations in 63 families from Tyrol. Clin Genet 52:240–246. .
- 1998. Case report of a Tai male cystic fibrosis patient with the 1998+1GT splicing mutation in the CFTR gene: a review of East Asian cases. Hum Mutat 12:361. .
- 1996. Geographic distribution and origin of CFTR mutations in Germany. Hum Genet 97:727–731. .
- 1997. Characterization of more than 85% of cystic fibrosis alleles in the Greek population, including five novel mutations. Hum Genet 99:121–125. .
- US Census Bureau. 1990. Race and Hispanic origin population density of the United States: 1990.www.census.gov/geo/www/mapGallery/RHOriginPD-1990.html.
- US Census Bureau. 2000a. American fact finder: thematic maps section. http://factfinder.census.gov/.
- US Census Bureau. 2000b. Census of population and housing: 2000. www.census.gov/prod/cen2000/index.html.
- 1997. Analysis of 16 cystic fibrosis mutations in Mexican patients. Am J Med Genet 69:380–382. .
- 1999. Clinical outcomes of newborn screening for cystic fibrosis. Arch Dis Child Fetal Neonatal Ed 80:F1–F7. .
- 1995. Cystic fibrosis. The metabolic and molecular bases of inherited disease. 17th ed. New York: McGraw-Hill. p 3799–3876. .
- 1995. Neonatal screening for cystic fibrosis: a comparison of two strategies for case detection in 1. 2 million babies. J Pediatr 127:965–970. .
- 2001. Comprehensive mutation screening in a cystic fibrosis center. Pediatrics 107:280–286. .
- 2000. Novel cystic fibrosis mutation L1093P: functional analysis and possible Native American origin. Hum Mutat 15:208. .
- 1995. Study of 12 mutations in Turkish cystic fibrosis patients. Hum Hered 45:175–177. .
- 1993. Identification of the M1101K mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and complete detection of cystic fibrosis mutations in the Hutterite population. Am J Hum Genet 52:609–615. .
- 1995. Cystic fibrosis: genotypic and phenotypic variations. Ann Rev Genet 29:777–807. .