title: Mutation spectrum in Jewish cystic fibrosis patients in Israel: implication to carrier screening.
abstract: 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 (DeltaF508, 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.
authors.affiliation: Department of Human Genetics, Hadassah Hebrew University Medical Hospital, Jerusalem, Israel.
authors.forename: Adina
authors.initials: A
authors.lastname: Quint
authors.forename: Israela
authors.initials: I
authors.lastname: Lerer
authors.forename: Michal
authors.initials: M
authors.lastname: Sagi
authors.forename: Dvorah
authors.initials: D
authors.lastname: Abeliovich
mesh_terms: D003550:Cystic Fibrosis / Q000208:ethnology / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D004252:DNA Mutational Analysis; D006580:Genetic Carrier Screening; D006115:Greece / Q000208:ethnology; D006801:Humans; D007492:Iran / Q000208:ethnology; D007493:Iraq / Q000208:ethnology; D007557:Israel / Q000453:epidemiology; D007585:Jews / Q000208:ethnology / Q000235:genetics*; D009018:Morocco / Q000208:ethnology; D009154:Mutation; D018807:Polymorphism, Single-Stranded Conformational; D014416:Tunisia / Q000208:ethnology; D014421:Turkey / Q000208:ethnology; D015006:Yemen / Q000208:ethnology
chemical_list: C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator