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Mutation spectrum in Jewish cystic fibrosis patients in Israel: Implication to carrier screening
Author(s) -
Quint Adina,
Lerer Israela,
Sagi Michal,
Abeliovich Dvorah
Publication year - 2005
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.30823
Subject(s) - single strand conformation polymorphism , genetics , allele , cystic fibrosis , mutation , founder effect , coding region , judaism , compound heterozygosity , population , medicine , microbiology and biotechnology , biology , gene , haplotype , history , environmental health , archaeology
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 (ΔF508, 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. © 2005 Wiley‐Liss, Inc.