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American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1992 Dec;51(6):1344–1348.

Ethnic heterogeneity and cystic fibrosis transmembrane regulator (CFTR) mutation frequencies in Chicago-area CF families.

C Ober 1, L A Lester 1, C Mott 1, C Billstrand 1, A Lemke 1, K van der Ven 1, S Marcus 1, J Kraut 1, J Lloyd-Still 1, C Booth 1
PMCID: PMC1682924  PMID: 1281385

Abstract

The identification of a common mutation, delta F508, in the CFTR gene allowed, for the first time, the detection of cystic fibrosis (CF) carriers in the general population. Further genetic studies revealed > 100 additional disease-causing mutations in this gene, few of which occur on > 1% of CF chromosomes in any ethnic group. Prior to establishing counseling guidelines and carrier risk assessments, we sought to establish the frequencies of the CFTR mutations that are present in CF families living in the Chicago area, a region notable for its ethnic heterogeneity. Our sample included 283 unrelated CF carriers, with the following ethnic composition: 78% non-Ashkenazi Caucasians, 5% Ashkenazi, 9% African-American, 3% Mexican, 0.3% Native American, and 5% mixed ancestry. When a panel of 10 mutations (delta F508, delta I507, G542X, G551D, R553X, S549N, R1162X, W1282X, N1303K, and 1717-1G-->A) was used, detection rates ranged from 75% in non-Ashkenazi Caucasians to 40% in African-Americans. These data suggest that the goal of screening for 90%-95% of CF mutations may be unrealistic in this and other, similar U.S. populations.

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Selected References

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  1. Caskey C. T., Kaback M. M., Beaudet A. L. The American Society of Human Genetics statement on cystic fibrosis screening. Am J Hum Genet. 1990 Feb;46(2):393–393. [PMC free article] [PubMed] [Google Scholar]
  2. Cutting G. R., Kasch L. M., Rosenstein B. J., Zielenski J., Tsui L. C., Antonarakis S. E., Kazazian H. H., Jr A cluster of cystic fibrosis mutations in the first nucleotide-binding fold of the cystic fibrosis conductance regulator protein. Nature. 1990 Jul 26;346(6282):366–369. doi: 10.1038/346366a0. [DOI] [PubMed] [Google Scholar]
  3. Gasparini P., Nunes V., Savoia A., Dognini M., Morral N., Gaona A., Bonizzato A., Chillon M., Sangiuolo F., Novelli G. The search for south European cystic fibrosis mutations: identification of two new mutations, four variants, and intronic sequences. Genomics. 1991 May;10(1):193–200. doi: 10.1016/0888-7543(91)90500-e. [DOI] [PubMed] [Google Scholar]
  4. Guillermit H., Fanen P., Ferec C. A 3' splice site consensus sequence mutation in the cystic fibrosis gene. Hum Genet. 1990 Sep;85(4):450–453. doi: 10.1007/BF02428306. [DOI] [PubMed] [Google Scholar]
  5. Kerem B. S., Zielenski J., Markiewicz D., Bozon D., Gazit E., Yahav J., Kennedy D., Riordan J. R., Collins F. S., Rommens J. M. 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 Nov;87(21):8447–8451. doi: 10.1073/pnas.87.21.8447. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Kerem B., Rommens J. M., Buchanan J. A., Markiewicz D., Cox T. K., Chakravarti A., Buchwald M., Tsui L. C. Identification of the cystic fibrosis gene: genetic analysis. Science. 1989 Sep 8;245(4922):1073–1080. doi: 10.1126/science.2570460. [DOI] [PubMed] [Google Scholar]
  7. Lemna W. K., Feldman G. L., Kerem B., Fernbach S. D., Zevkovich E. P., O'Brien W. E., Riordan J. R., Collins F. S., Tsui L. C., Beaudet A. L. Mutation analysis for heterozygote detection and the prenatal diagnosis of cystic fibrosis. N Engl J Med. 1990 Feb 1;322(5):291–296. doi: 10.1056/NEJM199002013220503. [DOI] [PubMed] [Google Scholar]
  8. Nunes V., Gasparini P., Novelli G., Gaona A., Bonizzato A., Sangiuolo F., Balassopoulou A., Giménez F. J., Dognini M., Ravnik-Glavac M. Analysis of 14 cystic fibrosis mutations in five south European populations. Hum Genet. 1991 Oct;87(6):737–738. doi: 10.1007/BF00201737. [DOI] [PubMed] [Google Scholar]
  9. Osborne L., Knight R., Santis G., Hodson M. A mutation in the second nucleotide binding fold of the cystic fibrosis gene. Am J Hum Genet. 1991 Mar;48(3):608–612. [PMC free article] [PubMed] [Google Scholar]
  10. Riordan J. R., Rommens J. M., Kerem B., Alon N., Rozmahel R., Grzelczak Z., Zielenski J., Lok S., Plavsic N., Chou J. L. Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science. 1989 Sep 8;245(4922):1066–1073. doi: 10.1126/science.2475911. [DOI] [PubMed] [Google Scholar]
  11. Rommens J. M., Iannuzzi M. C., Kerem B., Drumm M. L., Melmer G., Dean M., Rozmahel R., Cole J. L., Kennedy D., Hidaka N. Identification of the cystic fibrosis gene: chromosome walking and jumping. Science. 1989 Sep 8;245(4922):1059–1065. doi: 10.1126/science.2772657. [DOI] [PubMed] [Google Scholar]
  12. Shoshani T., Augarten A., Gazit E., Bashan N., Yahav Y., Rivlin Y., Tal A., Seret H., Yaar L., Kerem E. Association of a nonsense mutation (W1282X), the most common mutation in the Ashkenazi Jewish cystic fibrosis patients in Israel, with presentation of severe disease. Am J Hum Genet. 1992 Jan;50(1):222–228. [PMC free article] [PubMed] [Google Scholar]
  13. 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 Sep;85(4):446–449. doi: 10.1007/BF02428305. [DOI] [PubMed] [Google Scholar]

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