ABCMdb

PMID: 15948195

Quint A, Lerer I, Sagi M, Abeliovich D
Mutation spectrum in Jewish cystic fibrosis patients in Israel: implication to carrier screening.
Am J Med Genet A. 2005 Jul 30;136(3):246-8., 2005-07-30 [PubMed]

Sentences

No. Mutations Sentence Comment

6 ABCC7 p.Ile1234Val We identified three mutations in two or more CF chromosomes, 2571 þ 1insT in Jews from Iraq, 3121-1G > A in patients from Kurdistan and I1234V in Yemenite Jewish patients. Login to comment 25 ABCC7 p.Trp1282* ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Ser549Arg ABCC7 p.Gly85Glu ABCC7 p.Tyr1092* ABCC7 p.Asp1152His ABCC7 p.Trp1089* MUTATION ANALYSIS The following mutations are routinely tested in Jewish patients: the Ashkenazi founder mutations, DF508, W1282X, N1303K, G542X, 3849 þ 10 kb C!T, 1717-1G > A [Abeliovich et al., 1992], mutations commonly found in non-Ashkenazi patients, S549R (T!G), G85E, 405 þ 1G!A, W1089X, Y1092X, D1152H. Login to comment 26 ABCC7 p.Thr360Lys ABCC7 p.Gln359Lys The Q359K/T360K mutation is tested in patients from Georgia [Shoshani et al., 1993]. Login to comment 35 ABCC7 p.Trp1282* The founder mutations in the Ashkenazi patients accounted for 98.5% of the CF-bearing chromosomes; the major mutation was W1282X representing 43% of the CF mutations while DF508 mutation represented 33.5%. Login to comment 36 ABCC7 p.Asn1303Lys ABCC7 p.Gly542* The G542X, N1303K, 3849 þ 10 kb C!T, and 1717-1G!A mutations were found on 21.6% of the CF chromosomes. Login to comment 37 ABCC7 p.Ala455Glu ABCC7 p.Trp1282* ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Leu165Ser In this group we revealed two additional mutations L165S and A455E, each was identified on a single chromosome and one mutation remained unidentified. The relative frequencies of the Ashkenazi founder mutations in Ashkenazi patients were W1282X (43%), DF508 (33%), G542X (10%), 3849 þ 10 kb C!T (5%), N1303K (5%), and 1717 (1%). Login to comment 42 ABCC7 p.Gly1244Glu ABCC7 p.Leu997Phe ABCC7 p.Leu997Phe The L997F and G1244E mutations were identified following SSCP analysis, each on a single chromosome, and three alleles (9%) remain unidentified. The mutation L997F was described in patients with atypical CF [Castellani et al., 2001a,b] and patients with congenital absence of vas deferens [Dork et al., 1997] and it is debatable as to whether this is a CF-causing mutation or just a sequence variant. Login to comment 43 ABCC7 p.Trp1282* We tested 12 CF chromosomes of Tunisian origin, eight (66.7%) possessed the 405 þ 1G!A mutation, three DF508 and one had the W1282X mutation. Login to comment 44 ABCC7 p.Trp1282* ABCC7 p.Gly542* ABCC7 p.Gly85Glu ABCC7 p.Trp1089* Patients from the Balkan countries, Greece and Turkey (21 alleles), had some of the Ashkenazi founder mutations (W1282X, DF508, G542X, and 3849 þ 10 kb C!T), in addition to two other mutations, G85E and W1089X that were not found in Jewish patients from other origins. Login to comment 46 ABCC7 p.Tyr1092* Oriental Jews from Iraq (eight alleles) possessed the Y1092X mutation on three alleles. Login to comment 52 ABCC7 p.Thr360Lys ABCC7 p.Gln359Lys The patients from Georgia had the Q359K/T360K mutation on all their chromosomes. Login to comment 54 ABCC7 p.Trp1282* ABCC7 p.Ile1234Val Both had the I1234V mutation while the second mutation was DF508 in one patient and W1282X in the other. Login to comment 55 ABCC7 p.Ile1234Val We also identified the I1234V mutation in a patient with CBAVD and IVS8-5T variant on the second chromosome. Login to comment 57 ABCC7 p.Ile1234Val The I1234V mutation was described in Arab patients from the Arabian peninsula [Claustres et al., 1992; Kambouris et al., 2000] and several homozygous patients from a Beduin tribe in Qatar were described with variable clinical manifestations TABLE I. Login to comment 58 ABCC7 p.Ala455Glu ABCC7 p.Trp1282* ABCC7 p.Gly1244Glu ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Ser549Arg ABCC7 p.Gly85Glu ABCC7 p.Tyr1092* ABCC7 p.Asp1152His ABCC7 p.Met952Ile ABCC7 p.Ile1234Val ABCC7 p.Leu997Phe ABCC7 p.Trp1089* ABCC7 p.Thr360Lys ABCC7 p.Gln359Lys ABCC7 p.Leu165Ser Mutations in the CF Bearing Alleles in the Jewish Patients According to the Ethnic Origin Country of origin Ashkenazi Morocco Tunisia Balkan Iraq Iran/ Kurdistan Georgia Yemen Total Number of alleles (%) 193 (69.0) 34 (12.1) 12 (4.3) 21 (7.5) 8 (2.8) 3 (0.7) 8 (2.8) 2 (0.7) 281 W1282X (%) 83 (42.8) 1 (8.3) 4 (19.0) 88 (31.3) DF508 (%) 65 (33.5) 24 (70.6) 3 (25.0) 7 (33.3) 1 100 (35.6) N1303K (%) 10 (5.2) 10 (3.6) G542X (%) 19 (10.3) 4 (19.0) 24 (8.5) 3849-10 kbC!T (%) 10 (5.1) 1 (2.9) 2 (9.5) 13 (4.6) 1717-1G!A (%) 2 (1.0) 2 (0.7) D1152H (%) 1 (0.5) 1 (0.4) S549R (T!G) (%) 4 (11.8) 4 (1.4) G85E (%) 2 (9.5) 2 (0.7) 405 þ 1G!A (%) 8 (66.7) 8 (2.8) Y1092X (%) 3 (37.5) 3 (1.1) W1089X (%) 2 (9.5) 2 (0.7) Q359K/T360K (%) 8 (100) 8 (2.8) I1234V (%) 2 (100) 2 (0.7) 2751 þ 1insT (%) 2 (25.0) 2 (0.7) 3121-1G > A (%) 1 1 (0.4) M952I (%) 1 (12.5) 1 (0.4) L165S (%) 1 (0.5) 1 (0.4) A455E (%) 1 (0.5) 1 (0.4) L997F (%) 1 (2.9) 1 (0.4) G1244E (%) 1 (2.9) 1 (0.4) Unkown (%) 1 (0.5) 3 (8.8) 2 (25.0) 1 7 (2.5) Mutation Spectrum in Jewish CF Patients [Wahab, 2003]. Login to comment 59 ABCC7 p.Ile1234Val We found the mutation I1234V in 1 of 120 anonymous Yemenite Jews. Login to comment 61 ABCC7 p.Asp1152His The IVS-8 5T variant and the D1152H mutation are both common in the general Jewish population (Ashkenazi and non-Ashkenazi). Login to comment 62 ABCC7 p.Asp1152His It is important to note that while the D1152H mutation is common (0.9%) in the general Jewish population [Orgad et al., 2001], it is rare among patients with classical CF. Login to comment 65 ABCC7 p.Asp1152His Therefore, we recommend that the D1152H mutation and IVS-8 5T variant not be included in the panel of mutations that are tested in the carrier-screening program, a recommendation that was adopted by the Israeli Medical Genetic Organization. Login to comment 69 ABCC7 p.Trp1282* ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Ser549Arg ABCC7 p.Gly85Glu ABCC7 p.Tyr1092* ABCC7 p.Ile1234Val ABCC7 p.Trp1089* ABCC7 p.Thr360Lys ABCC7 p.Gln359Lys We suggest that 15 mutations that were found on two or more CF chromosomes from unrelated patients (DF508, W1282X, N1303K, G542X, 3849 þ 10 kb C!T, 1717-1 G!A, S549R (T!G), G85E, 405 þ 1G!A, W1089X, Y1092X, 2751 þ 1insT, 3121-1G!A, Q359K/T360K, I1234V) be tested in the CF screening of all Jewish individuals regardless of their origin. Login to comment