Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Novel cystic fibrosis mutation associated with mild disease in Cypriot patients


Cyprus is an island in the eastern Mediter-ranean basin inhabited by people of Caucasian extraction, mostly Greek-Cypriots. The most common inherited disease among Caucasians is cystic fibrosis (CF). Although no careful scientific study had ever been done the impression was that CF was extremely rare among the Greek-Cypriots, with an incidence estimated at around 1∶30,000. About 2 years ago, we introduced molecular diagnostic methodology in an effort to assist clinicians in safer diagnosis of patients presenting with atypical CF symptomatology, and also for testing the hypothesis that mutations that cause milder phenotypes might be responsible for misdiagnosis or for missing entirely some cases of CF. Initial screening for ΔF508 revealed that it is indeed rare in the general population. Further screening of suspected CF patients revealed a novel mutation that converted leucine at position 346 to proline (L346P) in two unrelated families. The second CF mutation was ΔF508 and 1677delTA in the two families respectively, both reportedly associated with severe phenotypes. Yet our patients did not present with typical CF pictures possibly because of the dominant nature of this novel mild mutation in exon 7. Symptoms included failure to thrive, chest infections and electrolyte disturbances. These findings raise the possibility that Cyprus might have been spared very severe CF phenotypes but not cystic fibrosis transmembrane conductance regulator (CFTR) mutations.

This is a preview of subscription content, log in to check access.


  1. Angelicheva D, Boteva K, Jordanova A, Savov S, Kalaydjieva L, Kufardjieva A, Telatar M, Akarsubasi A, Tolun A, Demirkol M, Kurdoglu G, Koprubasi F, Aydogdu S, Constantinou-Deltas CD, Georgiou C, Ivaschenko T, Baranov V, Dean M (1993) Cystic fibrosis patients from the Black Sea region: the 1677delTA mutation

  2. Balassopoulou A, Loucopoulos 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 Genet 85:393–394

  3. Boat TF, Welsh MJ, Beaudet AL (1989) Cystic Fibrosis. In: Scriver CL, Beaudet AL, Sly WS, Valle D (eds) The metabolic basis of inherited disease, 6th edn. McGraw-Hill, New York, pp 2649–2680

  4. Borgo G, Mastella G, Gasparini P, Zorzanello A, Doro R, Pignatti PF (1990) Pancreatic function and gene deletion F508 in cystic fibrosis. J Med Genet 27:665–669

  5. Constantinou-Deltas CD, Georgiou C, Ioannou P, Angastiniotis M, Aristodemou E (1992) ΔF508 cystic fibrosis mutation appears very infrequently in the Greek-Cypriot community of Cyprus. Hum Mutat 1:503–505

  6. Dean M, White MB, Amos J, Gerrard B, Steward 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

  7. Gibson LE, Cooke RE (1959) A test for concentration of electrolytes in sweat in cystic fibrosis of the pancreas utilizing pilocarpine by iontophoresis. Paediatrics 23:545–549

  8. Gyllensten UB, Erlich HA (1988) Generation of single-stranded DNA by the polymerase chain reaction and its application to direct sequencing of the HLA-DQA locus. Proc Natl Acad Sci USA 85:7652–7656

  9. 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

  10. Kerem B, Rommens JM, Buchanan JA, Markiewicz D, Cox T, Chakravarti A, Buchwald M, Tsui L-C (1989) Identification of the cystic fibrosis gene: genetic analysis. Science 245:1073–1080

  11. Miller SA, Dykes DD, Polesky HF (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16:1215

  12. Newton CR, Graham A, Heptinstall LE, Powell SJ, Summers C, Kalsheker N, Smith JC, Markham AF (1989) Analysis of any point mutation in DNA. The amplification refractory mutation system (ARMS). Nucleic Acids Res 17:2503–2516

  13. Riordan JR, Rommens JM, Kerem B-S, Alon N, Rozmahel R, Grzelczak Z, Zielenski J, Lok S, Plausic N, Chon J-L, 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

  14. Rommens JM, Iannuzzi MC, Kerem B-S, Drumm ML, Melher G, Dean M, Rozmahel R, Cole JL, Kennedy D, Hidaka N, Zsiga M, Buchwald M, Riordan JR, Tsui L-C, Collins FS (1989) Identification of the cystic fibrosis gene: chromosome walking and jumping. Science 245:1059–1065

  15. Saiki RK, Scharf S, Faloona F, Mullis KB, Horn GT, Erlich HA, Arnheim N (1985) Enzymatic amplification of β-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. Science 230:1350–1354

  16. Sheffield VC, Beck JS, Kwitek AE, Sandstrom DW, Stone EM (1993) The sensitivity of single-strand conformation polymorphism analysis for the detection of single base substitutions. Genomics 6:325–332

  17. 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

Download references

Author information

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Boteva, K., Papageorgiou, E., Georgiou, C. et al. Novel cystic fibrosis mutation associated with mild disease in Cypriot patients. Hum Genet 93, 529–532 (1994).

Download citation


  • Proline
  • Cystic Fibrosis
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Cystic Fibrosis Patient
  • Mild Phenotype