Screening for Non-delta F508 Mutations in Five Exons of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Gene in Italy

Overview

Journal Am J Hum Genet

Publisher Cell Press

Specialty Genetics

Date 1991 Jun 1

PMID 1709778

Citations 18

Authors

M Devoto

P Ronchetto

P Fanen

J J Orriols

G Romeo

M Goossens

M Ferrari

C Magnani

M Seia

L Cremonesi

Affiliations

Soon will be listed here.

Abstract

Analysis of exons 10, 11, 14a, 15, and 20 of the cystic fibrosis transmembrane conductance regulator (CFTR) gene by denaturing-gradient-gel electrophoresis (DGGE) allowed the identification of mutations causing cystic fibrosis (CF) in 25 of 109 non-delta F508 chromosomes, as well as identification of a number of polymorphisms and sequence variations. Direct sequencing of the PCR fragments which showed an altered electrophoretic behavior not attributable to known mutations has led to the characterization of four new mutations, two in exon 11, and one each in exons 15 and 20. Screening for the different mutations thus far identified in our patients by the DGGE analysis and other independent methods should allow detection of about 70% of the molecular defects causing CF in Italy. Mutations located in exons 11 and 20 account for at least 30% of the non-delta F508 mutations present in Italian CF patients.

Citing Articles

A neutral variant involved in a complex CFTR allele contributes to a severe cystic fibrosis phenotype.

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P67L: a cystic fibrosis allele with mild effects found at high frequency in the Scottish population.

Gilfillan A, Warner J, Kirk J, Marshall T, Greening A, Ho L J Med Genet. 1998; 35(2):122-5.

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Effects of the delta F508 mutation on the structure, function, and folding of the first nucleotide-binding domain of CFTR.

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Analysis of the complete coding region of the CFTR gene in a cohort of CF patients from north-eastern Italy: identification of 90% of the mutations.

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References

Myers R, Maniatis T, LERMAN L . Detection and localization of single base changes by denaturing gradient gel electrophoresis. Methods Enzymol. 1987; 155:501-27. DOI: 10.1016/0076-6879(87)55033-9. View

Orita M, Iwahana H, Kanazawa H, Hayashi K, Sekiya T . Detection of polymorphisms of human DNA by gel electrophoresis as single-strand conformation polymorphisms. Proc Natl Acad Sci U S A. 1989; 86(8):2766-70. PMC: 286999. DOI: 10.1073/pnas.86.8.2766. View

Cutting G, Kasch L, Rosenstein B, Zielenski J, Tsui L, Antonarakis S . A cluster of cystic fibrosis mutations in the first nucleotide-binding fold of the cystic fibrosis conductance regulator protein. Nature. 1990; 346(6282):366-9. DOI: 10.1038/346366a0. View

White M, Amos J, Hsu J, Gerrard B, Finn P, Dean M . A frame-shift mutation in the cystic fibrosis gene. Nature. 1990; 344(6267):665-7. DOI: 10.1038/344665a0. View

Dean M, White M, Amos J, Gerrard B, Stewart C, Khaw K . Multiple mutations in highly conserved residues are found in mildly affected cystic fibrosis patients. Cell. 1990; 61(5):863-70. DOI: 10.1016/0092-8674(90)90196-l. View

SANGER F, Nicklen S, Coulson A . DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977; 74(12):5463-7. PMC: 431765. DOI: 10.1073/pnas.74.12.5463. View

Wilfond B, Fost N . The cystic fibrosis gene: medical and social implications for heterozygote detection. JAMA. 1990; 263(10):2777-83. View

Kobayashi K, Knowles M, Boucher R, OBrien W, Beaudet A . Benign missense variations in the cystic fibrosis gene. Am J Hum Genet. 1990; 47(4):611-5. PMC: 1683805. View

Rommens J, Iannuzzi M, Kerem B, Drumm M, Melmer G, Dean M . Identification of the cystic fibrosis gene: chromosome walking and jumping. Science. 1989; 245(4922):1059-65. DOI: 10.1126/science.2772657. View

10.

Kerem B, Zielenski J, Markiewicz D, Bozon D, Gazit E, Yahav J . Identification of mutations in regions corresponding to the two putative nucleotide (ATP)-binding folds of the cystic fibrosis gene. Proc Natl Acad Sci U S A. 1990; 87(21):8447-51. PMC: 54973. DOI: 10.1073/pnas.87.21.8447. View

11.

Cutting G, Kasch L, Rosenstein B, Tsui L, Kazazian Jr H, Antonarakis S . Two patients with cystic fibrosis, nonsense mutations in each cystic fibrosis gene, and mild pulmonary disease. N Engl J Med. 1990; 323(24):1685-9. DOI: 10.1056/NEJM199012133232407. View

12.

Beaudet A . Carrier screening for cystic fibrosis. Am J Hum Genet. 1990; 47(4):603-5. PMC: 1683791. View

13.

Cremonesi L, Ruocco L, Seia M, Russo S, Giunta A, Ronchetto P . Frequency of the delta F508 mutation in a sample of 175 Italian cystic fibrosis patients. Hum Genet. 1990; 85(4):400-2. DOI: 10.1007/BF02428276. View

14.

Guillermit H, Fanen P, Ferec C . A 3' splice site consensus sequence mutation in the cystic fibrosis gene. Hum Genet. 1990; 85(4):450-3. DOI: 10.1007/BF02428306. View

15.

Vidaud M, Fanen P, Martin J, Ghanem N, Nicolas S, Goossens M . Three point mutations in the CFTR gene in French cystic fibrosis patients: identification by denaturing gradient gel electrophoresis. Hum Genet. 1990; 85(4):446-9. DOI: 10.1007/BF02428305. View

16.

Sheffield V, Cox D, LERMAN L, Myers R . Attachment of a 40-base-pair G + C-rich sequence (GC-clamp) to genomic DNA fragments by the polymerase chain reaction results in improved detection of single-base changes. Proc Natl Acad Sci U S A. 1989; 86(1):232-6. PMC: 286438. DOI: 10.1073/pnas.86.1.232. View

17.

Myers R, Larin Z, Maniatis T . Detection of single base substitutions by ribonuclease cleavage at mismatches in RNA:DNA duplexes. Science. 1985; 230(4731):1242-6. DOI: 10.1126/science.4071043. View

18.

Attree O, Vidaud D, Vidaud M, Amselem S, Lavergne J, Goossens M . Mutations in the catalytic domain of human coagulation factor IX: rapid characterization by direct genomic sequencing of DNA fragments displaying an altered melting behavior. Genomics. 1989; 4(3):266-72. DOI: 10.1016/0888-7543(89)90330-3. View

19.

Theophilus B, Latham T, Grabowski G, SMITH F . Comparison of RNase A, a chemical cleavage and GC-clamped denaturing gradient gel electrophoresis for the detection of mutations in exon 9 of the human acid beta-glucosidase gene. Nucleic Acids Res. 1989; 17(19):7707-22. PMC: 334879. DOI: 10.1093/nar/17.19.7707. View

20.

Cotton R, Rodrigues N, Campbell R . Reactivity of cytosine and thymine in single-base-pair mismatches with hydroxylamine and osmium tetroxide and its application to the study of mutations. Proc Natl Acad Sci U S A. 1988; 85(12):4397-401. PMC: 280436. DOI: 10.1073/pnas.85.12.4397. View