Mutation spectrum in Jewish cystic fibrosis patients in Israel: Implication to carrier screening

被引:34
作者
Quint, A [1 ]
Lerer, I [1 ]
Sagi, M [1 ]
Abeliovich, D [1 ]
机构
[1] Hadassah Med Ctr, Dept Human Genet, Hosp Med, IL-91120 Jerusalem, Israel
关键词
CFTR gene; cystic fibrosis; mutation analysis; population screening; founder mutations; Jews;
D O I
10.1002/ajmg.a.30823
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
We have tested 144 unrelated Jewish patients suffering from the classical form of cystic fibrosis. The patients were screened for a panel of 12 mutations including the six Ashkenazi founder mutations (Delta F508, W1282X, N1303K, G542X, 3849 + 10 kb C -> T, 1717-1G > A) and six mutations that were found in non-Ashkenazi Jewish patients (S549R (T -> G), G85E, 405 + 1G -> A, W1089X, Y1092, and D1152H). Patients of Georgian origin were tested also for the Q359K/T360K mutation. In addition, all the patients were tested for the IVS-8 variant 9T/7T/5T. Of all the cystic fibrosis (CF)-bearing chromosomes, 94% (264/281) were accounted for by one of the known mutations, and none of the patients had the 5T allele of the IVS-8 variant. Single strand conformation polymorphism. (SSCP) analysis of the coding sequence of the CFTR gene followed by sequencing showed eight mutations on ten CF chromosomes, leaving seven chromosomes (2.5%) with unknown mutations. We identified three mutations in two or more CF chromosomes, 2571 + 1insT in Jews from Iraq, 3121-1G > A in patients from Kurdistan and I1234V in Yemenite Jewish patients. The other five mutations appeared on a single allele and are considered "private mutations." In this study we have identified 99% of CF alleles in Ashkenazi Jewish patients, 91% in Jews of North African origin and 75% in Jewish patients from Iraq. The significance of these findings to the population screening in Israel is discussed. (c) 2005 Wiley-Liss, Inc.
引用
收藏
页码:246 / 248
页数:3
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