Abstract
To initiate the complete characterization of mutations in the CFTR gene in Greek cystic fibrosis (CF) patients, we screened 184 patients for six relatively common mutations (AF 508, G542X, G551D, 621+1 G→T, N1303K, W1282X) using allele-specific hybridization and, in addition, analyzed exons 4, 5, 7, 8, 10, 11, 17b, 19, 20 and 21 using the method of denaturing gradient gel electrophoresis (DGGE). Six mutations accounted for 65.9% of the CF alleles in Greek patients, of which the ΔF 508 mutation had a frequency of 52.7%. A further 15 previously described mutations accounted for another 8.3% CF alleles and one previously undescribed mutation (3272-4A→G) was found in one chromosome. The W1282X mutation was not detected at all. Thus, so far, we have identified 21 mutations in the CFTR gene in Greek CF patients, accounting for 74.5% of the CF alleles.
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References
Abeliovich D, Lavon IP, Lerer I, Cohen T, Springer C, Avital A, Cutting GR (1992) Screening for five mutations detects 97% of cystic fibrosis (CF) chromosomes and predicts a carrier frequency of 1∶29 in the Jewish Ashkenazi population. Am J Hum Genet 51:951–956
Balassopoulou A, Loukopoulos D, Kollia P, Devoto M, Adam G, Arvanitakis S, Hadjisevastou H (1990) Cystic fibrosis in Greece: typing with DNA probes and identification of the common molecular defect. Hum Gent 85:393–395
Casals T, Nunes V, Palacio A, Gimenez J, Gaona A, Ibanez N, Morral N, Estivill X (1993) Cystic fibrosis in Spain: high frequency of mutation G542X in the Mediterranean coastal area. Hum Genet 91:66–70
Fanen P, Ghanem N, Vidaud M, Besmond C, Martin J, Costes B, Plassa F, Goossens M (1992) Molecular characterization of cystic fibrosis: 16 novel mutations identified by analysis of the whole cystic fibrosis conductance transmembrane regulator (CFTR) coding regions and splice junctions. Genomics 13:770–776
Gasparini P, Pignatti PF, Novelli G, Dallapiccola B, Nunes V, Casals T, Estivill X, Fernandez E, Balassopoulou A, Loukopoulos D, Lanviha J, Simova L, Komel R (1990) Mutation analysis in cystic fibrosis. N Engl J Med 323:62–63
Gyllenstein UB, Erlich HA (1988) Generation of single stranded DNA by the polymerase chain reaction and its application to direct sequencing of the HLA-DQ locus. Proc Natl Acad Sci USA 85:7652–7656
Kazazian HH Jr (1994) Population variation of common cystic fibrosis mutations. Hum Mutat 4: 167–177
Kerem B, Rommens JM, Buchanan JA, Markiewicz D, Cox TK, Chakravarti A, Buchwald M, Tsui LC (1989) Identification of the cystic fibrosis gene: genetic analysis. Science 245: 1073–1080
Kerem B, Zielenski J, Markiewicz D, Bozon D, Gazit E, Yahav J, Kennedy D, Riordan J, Collins F, Rommens J, Tsui LC (1990) Identification of mutations in regions corresponding to the 2 putative nucleotide (ATP)-binding folds of the cystic fibrosis gene. Proc Natl Acad Sci USA 87:8447–8451
Old JM, Higgs DR (1982) Methods in haematology. In: Weatherall DJ (ed) Gene analysis. Churchill Livingstone, London pp 74–102
Riordan JR, Rommens JM, Kerem B, Alon N, Rozmahel R, Grzelczak Z, Zielenski J, Lok S, Plavsic N, Chou J, Drumm M, Iannuzzi M, Collins F, Tsui LC (1989) Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science 245:1066–1073
Ristaldi MS, Pirastu M, Rosatelli C, Monni G, Erlich H, Saiki R, Cao A (1989) Prenatal diagnosis of β-thalassemia in Mediterranean populations by dot blot analysis with DNA amplification and allele specific oligonucleotide probes. Prenat Diagn 9:629–638
Rommens JM, Iannuzzi MC, Kerem B, Drumm LM, Melmer G, Dean M, Rozmahel R, Kennedy D, Hidaka N, Zsiga M, Buchwald M, Riordan JR, Tsui LC, Collins FS (1989) Identification of the cystic fibrosis gene: chromosome walking and jumping. Science 245: 1059–1065
The Cystic Fibrosis Genetic Analysis Consortium (1990) Worldwide survey of the AF 508 mutation — report from the Cystic Fibrosis Genetic Analysis Consortium. Am J Hum Genet 47:354–359
Tsui L-C (1992) Mutations and sequence variations detected in the cystic fibrosis transmembrane conductance regulator (CFTR) gene: a report from the cystic fibrosis genetic analysis consortium. Hum Mutat 1:197–203
Zielenski J, Rozmahel R, Bozon D, Kerem BS, Grzelczak Z, Riordan JR, Rommens J, Tsui LC (1991) Genomic DNA sequence of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Genomics 10:214–228
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Kanavakis, E., Tzetis, M., Antoniadi, T. et al. 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 (1995). https://doi.org/10.1007/BF00210426
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DOI: https://doi.org/10.1007/BF00210426