Abstract
Mutations of CFTR were studied in patients with cystic fibrosis (CF) from Bashkortostan. In total, 15 mutations were observed and 51% of all mutant alleles identified. The most diagnostically significant mutations were delF508 (33.8%), 394delTT (3.52%), CFTRdele2,3(21kb) (1.41%), R334W (1.41%), 3849 + 10kbC → T (1.41%), and N1303K (1.41%). Mutations G542X, 2184insA, S1196X, and W1282X were each found in less than 1% patients. Five new mutations and two neutral substitutions were revealed. These were I488M (exon 10), 1811 + 12A → C (intron 11), T663S (exon 13), I1226R (exon 19), 4005 + 9A → C (intron 20), 2097A → C (A655A, exon 13), and 3996G → C (V1288V, exon 20). Bashkortostan was shown to differ in the CFTR mutation spectrum from other regions of Russia. The results will allow direct DNA diagnostics of CF in far more families. Molecular screening of probands" relatives will contribute to identification and medical genetic counseling of heterozygous carriers, which is essential for CF prevention.
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REFERENCES
Kerem B., Rommens J.M., Buchanan J.A., et al. 1989. Identification of the cystic fibrosis gene: genetic analysis. Science. 245, 1073–1080.
Riordan J.M., Rommens J.M., Kerem B., et al. 1989. Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science. 245, 1066–1073.
Rommens J.M., Iannuzzi M.C., Kerem B., et al. 1989. Identification of cystic fibrosis gene: chromosome walking & jumping. Science. 245, 1059–1065.
Grubb B., Pikles R., Ye H., et al. 1994. Inefficient gene transfer by adenovirus vector to cystic fibrosis airway epitelia of mice and humans. Nature. 371, 802–806.
Stutts J., Canessa C., Olsen J., et al. 1995. CFTR as a camp-dependent regulator of sodium channels. Science. 269, 847–849.
Reddy M., Quinton P., Haws C., et al. 1996. Faiure of the cystic fibrosis transmembrane conductance regulator to conduct ATP. Science. 271, 1876–1879.
The CF mutation database 2002: http//www.genet.sickkids.on.cax/cftr
Bombieri C., Giorgi S., Carles S., et al. 2000. A new approach. For identifying non-patogenic mutations. An analysis of the cystic fibrosis transmembrane regulator gene in normal individuals. Human Genet. 106, 172–178.
Noone P., Zhou Z., Silverman L., et al. 2001. Cystic fibrosis gene mutations and pancreatitis risk: relation to epithelial ion transport and trypsin inhibitor gene mutations. Gastroenterology. 6, 1310–1319.
Tzetis M., Efhtymiadou A., Strofakis S., et al. 2001. CFTR gene mutations including three novel nucleotide susstitutions and haplotype backgraund in patients with astma, disseminated bronchiectasis and chronic obstructive pulmonary disease. Human Genet. 108, 216–221.
Chuchalin A.G., Voronina L.M., Kronina L.A., et al. 1994. Cystic fibrosis in adults: Etiology, pathogenesis, prospects of treatment. Pul'monologiya 3, 17–23.
Petrova N.V., Kapranov N.I., Ginter E.K. 1997. Analysis of the common mutations of the CFTR gene in cystic fibrosis patients from Central Russia. Genetika 33, 106–109.
Kapranov N.I., Kashirskaya N.Yu. 1998. Urgent problems in cystic fibrosis. Pediatriya 1, 61–66.
Mitkina E.N., Gembitskaya T.E., Fokina A.A., et al. 1999. Measuring the nasal potential difference: A new informative diagnostic test for cystic fibrosis. Pul'monologiya 3, 50–54.
Kapranov N.I. 2001. Achievements and current problems in diagnostics and treatments of cystic fibrosis in Russia. Pul'monologiya 11, 9–16.
Bayleran J.K., Yan H., Hopper C. A., et al. 1996. Frequencies of cystic fibrosis mutations in the Maine population of unknown alleles in individuals of French-Canadian ancestry. Human Genet. 98, 20–209.
Estivill X., Bancells C., Ramos C., et al. 1997. The Biomed CF Mutation Analysis Consortium: geographic distribution and regional origin of 272 cystic fibrosis mutations in European populations. Human Mutat. 10, 135–154.
Chiba-Falek O., Nissim-Rafinia M., Argaman Z., et al. 1998. Screning of CFTR mutations in an isolated population: identification of carriers and patients. Eur. J. Human Genet. 6, 181–184.
Onay T., Topaloglu O., Zielenski J., et al. 1998. Analysis of the CFTR gene in Turkish cystic fibrosis patients: identification of three novel mutations (3172delAC, P1013L and M1028I). Human Genet. 102, 224–230.
Ivashchenko T.E., Baranov V.S. 2002. Biokhimicheskie i molekulyarno-biologicheskie osnovy patogeneza mukovistsidoza (Biochemical and molecular biological bases of cystic fibrosis), St. Petersburg: Intermedika.
Petrova N.V. and Ginter E.K. 2001. Ten-year experience of molecular genetic diagnostics of cystic fibrosis in the Medical Genetic Research Center. Pul'monologiya 11, 17–20.
Baranov V.S., Baranova E.V. Ivashchenko T.E., Aseev M.V. 2000. Genom cheloveka i geny “predraspolozhennosti” (Vvedenie v prediktivnuyu meditsinu) (The human genome and predisposition genes: Introduction to predictive medicine), St. Petersburg: Intermedika.
Gorbunova V.N., Baranov V.S. 1997. Vvedenie v molekulyarnuyu diagnostiku i genoterapiyu nasledstvennykh zabolevanii (Introduction to molecular diagnostics and gene therapy of hereditary disorders). St. Petersburg: Spetsial'naya Literatura.
Zielenski J., Rosmahel R., Bozon D., et al. 1991. Genomic DNA sequence of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Genomics. 10, 214–228.
Sazonova M.A., Amosenko F.A., Kapranov N.I., et al. 1997. Molecular genetic analysis of the TUB18 and TUB20 intergenic polymorphisms and several mutations of the TRBM gene in the Moscow region. Genetika 33, 1303–1307.
Green E.D., Olson M.V. 1990. Chromosomal region of the cystic fibrosis gene in yeast artificial chromosomes: a model for human genom mapping. Science. 250, 94–98.
Abeliovich D., Lavon I.P., Lerer I., et al. 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. Human. Genet. 51, 951–956.
Orita M., Jwahana H., Kanazawa H., et al. 1989. Detection of polymorphism of human DNA by gel electrophoresis as single cell conformation polymorphism. Proc. Natl. Acad. Sci. USA. 86, 2766–2770.
Schwarz M., Anuret M., Claustres M., et al. 1994. 394delTT: a nordic CF mutation. Human Genet. 93, 157–161.
Glazkov P.B., Mitkina E.N., Gembitskaya T.E., et al. 2000. The genotype–phenotype relationships in patients and development of the experimental basis for gene therapy in cystic fibrosis. Pul'monologiya 1, 14–23.
Dork Th., Mekus B., Macek J., et al. 2000. Characterisation of a novel 21-kb deletion, CFTRdele2,3(21kb), in the CFTR gene: a cystic fibrosis mutation of Slavic origin common in Central and East Europe. Human Genet. 106, 259–268.
Morral N., Bertranpetit J., Estivill X. 1994. The origin of the major cystic fibrosis mutation (delF508) in European populations. Nature Genet. 7, 169–175.
Chiba-Falek O., Kerem E., Shoshani T., et al. 1998. The molecular basis of disease variability among cystic fibrosis patients carrying the 3849 + 10kb C → T mutation. Genomics. 53, 276–283.
Angelicheva D., Boteva K., Jordanova A., et al. 1994. Cystic fibrosis patients from the black sea region: the 1677delTA mutation. Human Mutat. 3, 353–357.
Dequeker E., Cuppens H., Dodge J., et al. 2000. Recommendations for quality improvement in genetic testing for cystic fibrosis European Concerted Action on cystic fibrosis. Europ. J. Human Genet. 8, 2–24.
Messaound T., Verlingue C., Denamur E., et al. 1996. Distribution of CFTR mutations in cystic fibrosis patients of Tunisian origin: identification of two novel mutations. Eur. J. Human Genet. 4, 20–24.
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Korytina, G.F., Viktorova, T.V., Ivashchenko, T.E. et al. The Mutation Spectrum of the CFTR Gene in Cystic Fibrosis Patients from Bashkortostan. Molecular Biology 37, 56–61 (2003). https://doi.org/10.1023/A:1022380729131
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DOI: https://doi.org/10.1023/A:1022380729131