Summary
The N1303K mutation was identified in the second nucleotide binding fold of the cystic fibrosis (CF) gene last year. We have gathered data from laboratories throughout Europe and the United States of America in order to estimate its frequency and to attempt to characterise the clinical manifestations of this mutation. N1303K, identified on 216 of nearly 15000 CF chromosomes tested, accounts for 1.5% of all CF chromosomes. The frequency of the N1303K allele varies significantly between countries and ethnic groups, being more common in Southern than in Northern Europe. This variation is independent of the AF508 allele. It was not found on UK Asian, American Black or Australian chromosomes. N1303K is associated with four different linked marker haplotypes for the polymorphic markers XV-2c, KM.19 and pMP6d-9. Ten patients are homozygous for this mutation, whereas 106 of the remainder carry one of 12 known CF mutations in the other CF allele. We classify N1303K as a “severe” mutation with respect to the pancreas, but can find no correlation between this mutation, in either the homozygous or heterozygous state, and the severity of lung disease.
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Bal J, Rininsland F, Osborne L, Reiss J (1992) Simple non-radioactive detection of the CFTR mutation N1303K by artificial creation of a restriction site. Mol Cell Probes 6:9–11
Cutting GR, Kasch LM. Rosenstein BJ, Zielenski J, Tsui L-C, Antonarakis SE, Kazazian HH (1990a) A cluster of cystic fibrosis mutations in the first nucleotide-binding fold of the cystic fibrosis conductance regulator protein. Nature 346:366–369
Cutting GR, Kasch LM, Rosenstein BJ, Tsui L-C, Kazazian HH, Antonarakis SE (1990b) Two patients with cystic fibrosis, nonsense mutations in each cystic fibrosis gene, and mild pulmonary disease. N Engl J Med 323:1517–1522
Dean M, White MB, 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
Friedman KJ, Highsmith Jr WE, Silverman LM (1991) Detecting multiple cystic fibrosis mutations by polymerase chain reaction-mediated site-directed mutagenesis. Clin Chem 37:753–755
Gasparini P, Nunes V, Savoia A, Dognini M, Morral N, Gaona A, Bonizzato A, Chillon M, Sangiuolo F, Novelli G, Dallapiccola B, Pignatti PF, Estivill X (1991) The search for South European cystic fibrosis mutations: identification of two new mutations, four variants, and intronic sequences. Genomics 10:193–200
Gregory RJ, Rich DP, Cheng SH, Souza DW, Paul S, Manavalan P, Anderson MP, Welsh MJ, Smith AE (1991) Maturation and function of cystic fibrosis transmembrane conductance regulator variants bearing mutations in putative nucleotide-binding domains 1 and 2. Mol Cell Biol 11:3886–3893
Guillermit H, Fanen P, Ferec C (1990) A 3′ splice site consensus sequence mutation in the cystic fibrosis gene. Hum Genet 85:450–453
Iannuzzi MC, Stern RC, Collins FS, Tom Hon C, Hidaka N, Strong T, Becker L, Drumm ML, White MB, Gerrard B, Dean M (1991) Two frameshift mutations in the cystic fibrosis gene. Am J Hum Genet 48:227–231
Ivaschenko TE, 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, Rommens JM, Buchanan JA, Markiewicz D, Coz TK, Chakravarti A, Buchwald M, Tsui L-C (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 JR, Collins FS, Rommens JM, Tsui L-C (1990) Identification of mutations in regions corresponding to the two putative nucleotide (ATP)-binding folds of the cystic fibrosis gene. Proc Natl Acad Sci USA 87:8447–8451
Kerem E, Corey M, Kerem B-S, Rommens J, Markiewicz D, Levison H, Tsui L-C, Durie P (1990) The relation between genotype and phenotype in cystic fibrosis-analysis of the most common mutation (δF508). N Engl J Med 323:1517–1522
Ng ISL, Pace R, Richard MV, Kobayashi K, Kerem B, Tsui L-C, Beaudet AL (1991) Methods for analysis of multiple cystic fibrosis mutations. Hum Genet 87:613–617
Osborne L, Knight R, Santis G, Hodson ME (1991) A mutation in the second nucleotide-binding fold of the cystic fibrosis gene. Am J Hum Genet 48:608–612
Riordan JR, Rommens JM, Kerem B, Alon N, Rozmahel R, Grzelczak Z, Zielenski J, Lok S, Plavsic N, Drumm ML, Iannuzzi MC, Collins FS, Tsui L-C (1989) Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science 245:1066–1073
Santis G, Osborne L, Knight R, Hodson ME (1990a) Linked marker haplotypes and the δF508 mutation in adults with mild pulmonary disease and cystic fibrosis. Lancet 335:1426–1429
Santis G, Osborne L, Knight R, Hodson ME (1990b) Independent genetic determinants of pancreatic and pulmonary status in cystic fibrosis. Lancet 336:1081–1084
Shoshani T, Bashan N, Augarten A, Gazit E, Yahav, Rivlin Y. Kerem E, Kerem B (1991) A termination mutation (W1282X). the most common mutation in the Jewish Ashkenazi CF patients in Israel, is associated with a severe disease presentation. Pediatr Pulmunol Suppl 6:242
Vidaud M, Fanen P, Martin J, Ghanem N, Nicolas S, Goossens M (1990) Three point mutations in the CFTR gene in French cystic fibrosis patients: identification by denaturing gradient gel electrophoresis. Hum Genet 85:446–449
White MB, Amos J, Hsu JMC, Gerrard B, Finn P, Dean M (1990) A frame-shift mutation in the cystic fibrosis gene. Nature 344: 665–667
White MB, Krueger LJ, Holsclaw DS, Gerrard BC, 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 (CF444de1A), an Italian (CF2522insC), and a Soviet (CF3821delT). Genomics 10:266–269
Zielenski J, Bozon D, Kerem B, Markiewicz D, Durie P, Rommens JM, Tsui L-C (1991) Identification of mutations in exons 1 through 8 of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Genomics 10:229–235
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Osborne, L., Santis, G., Schwarz, M. et al. Incidence and expression of the N1303K mutation of the cystic fibrosis (CFTR) gene. Hum Genet 89, 653–658 (1992). https://doi.org/10.1007/BF00221957
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DOI: https://doi.org/10.1007/BF00221957