Abstract
Single-strand conformation polymorphism (SSCP) analysis followed by direct sequencing of exons containing ATP-binding domains of the cystic fibrosis transmembrane conductance regulator (CFTR) gene was performed on 80 Russian DNA samples. Two new alterations — S1196X (exon 19) and W1282R (exon 20) — and two novel polymorphisms — 1525-61 (intron 9) and 1716+12 T-C (intron 10) — were identified. Mutation S1196X changes a TCA codon to TGA and destroys an EcoRI site. Alteration W1282R results from a T-to-C change at position 3976. It was found in one Russian patient and creates an AciI site; however, it is unclear whether this is a disease-causing mutation or a polymorphism. Polymorphism 1525-61 results from an A-to-G change. Alteration 1716+12 T-C was found in a Moldovian patient and creates a new MaeII site. It is not known whether this alteration affects the splicing of the mRNA. The previously described A4002G polymorphism was encountered in approximately 9% of Russian CF chromosomes. In addition, we have found the previously described 3732delA mutation in 7 CF chromosomes, making it the second (after ΔF508) most frequent mutation in the Russian population.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Baranov VS, Ivaschenko TE, Borbunova VN, Dean M (1990) The frequency of F508 deletion of the mucoviscidosis gene in patients and in families at high risk in Soviet populations. Dokl Akad Nauk SSSR 313:446–448
Baranov VS, Ivaschenko TE, Gorbunova VN, Livshitz LA, Venozinskis MT, Gembovskaya SA, Kalinin VN, Romanenko OP, Gembitzkaya TE, Orlov AV, Kapranov NN, Lebedev VM, Mihailov AV, Pigina TV, Shwed NY (1991a) Frequency of the F508 deletion in cystic fibrosis patients from the European part of the USSR. Hum Genet 87:61–64
Baranov VS, Ivaschenko TE, Gorbundova VN, Osynovskaya N, Gimbovskaya SD (1991b) Five years experience in the molecular analysis of cystic fibrosis in the USSR. Pediatr Pulmonol 6 [Suppl]:244
Claustres M, Gerrard B, Kjellberg P, Desgorges M, Demaille J, Dean M (1992) Screening for cystic fibrosis mutations in southern France: identification of a frameshift mutation and two missense variations. Hum Mutat 1:310–313
Cutting GP, Kasch LM, Rosenstein BJ, Zielenski I, Tsui LC, Antonarakis SF, Kazazian HH Jr (1990) A cluster of cystic fibrosis mutations in the first nucleotide-binding fold of the cystic fibrosis conductance regulator protein. Nature 346:336–369
Dean M, Gerrard B (1991) Helpful hints for the detection of single-stranded conformation polymorphisms. Biotechniques 10:332–333
Dean M, White M, Amos J, Gerrard B, Stewart C, Khaw K-T, Leppert M (1990) Multiple mutations in highly conserved residues are found in mildly affected cystic fibrosis patients. Cell 61:863–870
Ivaschenko E, White MB, Dean M, Baranov VS (1991) A deletion of two nucleotides in exon 10 of the CFTR gene in a soviet family with cystic fibrosis causing early infant death. Genomics 10:298–299
Kerem B, Zielenski J, Markiewicz D, Bozon D, Gazit E, Yahaf J, Kennedy D, Riordan JR, Collins FS, Rommens JR, Tsui L-C (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
Kobayashi K, Knowles M, O'Brien WE, Beaudet AL (1990) Benign missense variations in the cystic fibrosis gene. Am J Hum Genet 47:611–615
Osborne K, Knight RA, Santis G, Hodson M (1991) A mutation in the second nucleotide binding fold of the cystic fibrosis gene. Am J Hum Genet 48:608–612
Tsui LC (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
Vidaud M, Fanen P, Martin J, Ghanem N, Nicolas S, Goossens M (1990) Three mutations in the CFTR gene in French cystic fibrosis patients: identification by denaturing gradient gel electrophoresis. Hum Genet 85:446–449
White MB, Krueger LJ, Holsclaw DS Jr, Gerrard B, Stewart C, Quittell L, Dolganov G, Baranov V, Ivaschenko T, Kapronov NI, Sebastio G, Castiglione O, Dean M (1991) Detection of three rare frameshift mutations in the cystic fibrosis gene in an African-American (CF444delA), Italian (CF2522insC), and a Soviet (CF3821delT). Genomics 10:266–269
Zielenski J, Rozmahel R, Bozon D, Kerem B, Grzelczak Z, Riordan JR, Rommens JM, Tsui L-C (1991) Genomic DNA sequence of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Genomics 10:214–228
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ivaschenko, T.E., Baranov, V.S. & Dean, M. Two new mutations detected by single-strand conformation polymorphism analysis in cystic fibrosis from Russia. Hum Genet 91, 63–65 (1993). https://doi.org/10.1007/BF00230224
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00230224