Ober C, Lester L A, Mott C, Billstrand C, Lemke A, van der Ven K, Marcus S, Kraut J, Lloyd-Still J, Booth C
Department of Obstetrics and Gynecology, University of Chicago, IL 60637.
Am J Hum Genet. 1992 Dec;51(6):1344-8.
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.
CFTR基因中常见突变ΔF508的鉴定，首次使得在普通人群中检测囊性纤维化（CF）携带者成为可能。进一步的遗传学研究揭示，该基因还有100多个致病突变，在任何种族群体中，这些突变很少出现在超过1%的CF染色体上。在制定咨询指南和携带者风险评估之前，我们试图确定居住在芝加哥地区（一个以种族异质性著称的地区）的CF家族中存在的CFTR突变频率。我们的样本包括283名无亲缘关系的CF携带者，其种族构成如下：78%为非阿什肯纳兹白人，5%为阿什肯纳兹人，9%为非裔美国人，3%为墨西哥人，0.3%为美洲原住民，5%为混合血统。当使用一组10种突变（ΔF508、ΔI507、G542X、G551D、R553X、S549N、R1162X、W1282X、N1303K和1717-1G→A）时，检测率从非阿什肯纳兹白人中的75%到非裔美国人中的40%不等。这些数据表明，在美国这个群体以及其他类似群体中，筛查90%-95%的CF突变这一目标可能不切实际。
