ABCMdb

PMID: 11336401

Orgad S, Neumann S, Loewenthal R, Netanelov-Shapira I, Gazit E
Prevalence of cystic fibrosis mutations in Israeli Jews.
Genet Test. 2001 Spring;5(1):47-52., [PubMed]

Sentences

No. Mutations Sentence Comment

33 ABCC7 p.Trp1282* ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Ser549Arg ABCC7 p.Gly85Glu ABCC7 p.Asp1152His ABCC7 p.Trp1089* These were: delF508 (Kerem et al., 1989), W1282X (Vidaud et al., 1990), G542X, 1717-1G R A, S549R (Kerem et al., 1990), N1303K (Osborn et al., 1991), 3849 1 10Kb C R T (Highsmith et al., 1994), T359K/Q360K (Shoshani et al., 1992), G85E (Zielenski et al., 1991), 405 1 1G R A (Dork et al., 1993), W1089X (Shosani et al., 1994), and D1152H (Highsmith et al., 1993). Login to comment 40 ABCC7 p.Trp1282* ABCC7 p.Asn1303Lys ABCC7 p.Ser549Arg ABCC7 p.Gly85Glu ABCC7 p.Asp1152His ABCC7 p.Trp1089* ABCC7 p.Thr360Lys THE CONSENSUS POLICY OF SCREENING OF CF MUTATIONS IN ETHNIC GROUPS OF ISRAELI JEWSa Buchara and Iran Georgia Libya Morocco Tunis Turkey Egypt Sephardi W1089X 1 1 1 G85E 1 1 405-1 G® A 1 1 1 S549R 1 1 D1152H 1 1 1 1 T360K 1 Individuals of all ethnic groups were screened for the mutations W1282X, delF508, G5429X, N1303K, 3849110Kb C® T and 1717-1G® A. Login to comment 45 ABCC7 p.Trp1282* ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Ser549Arg ABCC7 p.Gly85Glu ABCC7 p.Asp1152His ABCC7 p.Trp1089* ABCC7 p.Thr360Lys There were 173 (46.3%) carriers of the W1282X mutation; 110 (29.4%) carriers of delF508; 23 (6.1%) carriers of G542X; 10 (2.7%) carriers of N1303K; and 22 (5.9%) carriers of 3849 1 10KbC R T. Twenty (5.3%) were found to carry D1152H; 11 (2.9%) carried 405 1 1G R A; 4 (1.1%) carried W1089X; and 1 (0.3%) carried S549R. No carriers were detected for the mutations 1717-1G R A, G85E, and T360K, which were tested for in 7,383, 1,436, and 41 individuals, respectively. Login to comment 46 ABCC7 p.Asp1152His ABCC7 p.Trp1089* D1152H, W1089X, and 405 1 1G R A were tested for in 2,764, 1,658, and 1,551 individuals, respectively. Login to comment 47 ABCC7 p.Asp1152His ABCC7 p.Trp1089* The mutations D1152H and W1089X were detected in individuals whose origins had not been included in the consensus panel policy, namely Ashkenazi and Eastern Jews (Table 4B; Figs. 1 and 2). Login to comment 52 ABCC7 p.Trp1282* ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Ser549Arg ABCC7 p.Asp1152His ABCC7 p.Trp1089* Mutations tested for all individuals in the cohort North Total Ashkenazi Sephardi Africa Eastern number of Mutation no. 6850 no. 933 no. 1146 no. 468 carriers W1282X 142 17 8 6 173 delF508 86 12.25 11.5 0.25 110 G542X 20.25 0.5 1.75 0.5 23 N1303K 7.5 1.5 0.25 0.75 10 3849110Kb 17 2 2 1 22 C® T B. Mutations tested for individuals of non-Ashkenazi origin, mixed origin, and of spouses of carriers Type of Total number mutation Number tested Ashkenazi Sephardi North Africa Eastern of carriers D1152H Number tested 1,305 458.25 722.75 280 Carriers 11.5 4.5 3.5 0.5 20 405 Number tested 425.75 372 633.5 119 11G® A Carriers 0.5 1 9.5 0 11 W1089X Number tested 539.25 345 638.5 135 Carriers 2 0.5 1 0.5 4 S549R Number tested 534.5 385.5 686 110 Carriers 0 1 0 0 1 a Ethnic origin was classified according to the country of origin of the four grandparents of each individual. Each grandparent was calculated as contributing a quarter of his/her gene pool and these were summed up for each ethnic origin. Login to comment 54 ABCC7 p.Asp1152His Ethnic origin of carriers of the D1152H mutation. Login to comment 55 ABCC7 p.Asp1152His The D1152H mutation was tested in 2,701 individuals; 20 were carriers (0.74%). Login to comment 61 ABCC7 p.Trp1089* Ethnic origin of carriers of the W1089X mutation. Login to comment 62 ABCC7 p.Trp1089* The W1089X mutation was tested in 1,615 individuals; 4 were carriers (0.24%). Login to comment 69 ABCC7 p.Trp1282* About half of the carriers had the W1282X and only about 30% carried the delF508 mutation. Login to comment 74 ABCC7 p.Trp1282* ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Asp1152His ABCC7 p.Trp1089* Therefore, Ashkenazi Jews would have been tested for the five main mutationsonly: delF508,W1282X, G542X, N1303K, and 3849 1 10KbC R T. The mutations D1152H and W1089X would not have been included in the test panel in Ashkenazi Jews. Login to comment 77 ABCC7 p.Asp1152His ABCC7 p.Asp1152His ABCC7 p.Trp1089* Surprisingly, our results show that the D1152H and W1089X mutations are present in Ashkenazi Jews, as 8 of the 20 carriers of D1152H were of Ashkenazi origin only, and an additional 6 were half-Ashkenazi (Table 4B; Figs. 1 and 2). Login to comment 78 ABCC7 p.Trp1089* Similarly, 1 Ashkenazi carrier and 1 half-Ashkenazi carrier were found among 4 carriers of W1089X. Login to comment 79 ABCC7 p.Asp1152His Of special interest is the D1152H mutation. Login to comment 85 ABCC7 p.Asp1152His It seems, therefore, that the D1152H mutation exists in all Jewish ethnic groups. Login to comment 86 ABCC7 p.Gly85Glu ABCC7 p.Thr360Lys On the other hand, some mutations that were found in CF patients were not detected in the healthy cohort we studied, namely, G85E, 1717-1G R A, and T360K. Login to comment 87 ABCC7 p.Thr360Lys It should be noted, however, that we tested only 41 Georgian Jews, and, if the frequency of T360K is around 1% in this ethnic group, it is not surprising that we did not detect it in such a small sample. Login to comment 91 ABCC7 p.Ser549Arg ABCC7 p.Gly85Glu ABCC7 p.Trp1089* One might reconsider the cost effectiveness of testing for infrequent mutations such as 1717-1G R A, W1089X, S549R, and G85E when screening the general Jewish population. Login to comment