ABCMdb

PMID: 1377276

Lerer I, Sagi M, Cutting GR, Abeliovich D
Cystic fibrosis mutations delta F508 and G542X in Jewish patients.
J Med Genet. 1992 Feb;29(2):131-3., [PubMed]

Sentences

No. Mutations Sentence Comment

0 ABCC7 p.Gly542* I Med Genet 1992 29: 131-133 Cystic fibrosis mutations AF508 and G542X in Jewish patients I Lerer, M Sagi, G R Cutting, D Abeliovich Abstract We have screened our CF patients for mutations in exons 10 and 11 of the CFTR gene. Login to comment 1 ABCC7 p.Gly542* Two mutations, AF508 and G542X, have been found in 66 Jewish CF patients. Login to comment 3 ABCC7 p.Gly542* The G542X mutation accounts for 13% of the Ashkenazi CF mutations and has been found in three out of seven chromosomes of Jewish patients from Turkey (probably descended from Ashkenazi immigrants). Login to comment 4 ABCC7 p.Gly542* The G542X mutation was not found in any of the other non-Ashkenazi patients. Login to comment 5 ABCC7 p.Gly542* All the G542X bearing chromosomes have the same haplotype. Login to comment 6 ABCC7 p.Gly542* Based on these observations it is concluded that the G542X mutation was introduced into the Jewish people after the split into Ashkenazi and non-Ashkenazi. Login to comment 8 ABCC7 p.Gly551Asp ABCC7 p.Arg553* ABCC7 p.Gly542* ABCC7 p.Ser549Asn The majority of these are rare mutations observed in single families but some mutations are relatively frequent.3 We have screened CF patients for the AF508 mutation and for G542X, G551D, R553X, and S549N or I, all within exon 11, and for the splice mutation 1717-1G-.A. Login to comment 9 ABCC7 p.Gly542* Two mutations have been found among the Jewish patients, AF508 and G542X. Login to comment 18 ABCC7 p.Gly542* Exon 11 was amplified by PCR using 1 li-5 and 1 i-3 as primers.3 The mutations G542X and 1717-1G--A were analysed by ASO hybridisation. Login to comment 20 ABCC7 p.Gly551Asp ABCC7 p.Arg553* G551D and R553X eliminate a HincII site. Login to comment 21 ABCC7 p.Ser549Asn S549N or I eliminates a DdeI site.4 RFLPs were analysed by either Southern blot hybridisation or by PCR. Login to comment 28 ABCC7 p.Arg553* Among the Ashkenazi families, the mother was not Jewish in one family (and had the R553X mutation) and in one family the patient was the result of uniparental disomy.7 Therefore, the total number of CF chromosomes was 127, ofwhich 84 chromosomes were of Ashkenazi origin and 43 of non-Ashkenazi origin. Login to comment 32 ABCC7 p.Gly542* The G542X mutation was found in 14 CF chromosomes, in 11 (13%) chromosomes of Ashkenazi origin and in three out of a total of seven (43%) chromosomes of Turkish origin. Login to comment 33 ABCC7 p.Gly542* None ofthe other Sephardic CF chromosomes had the G542X mutation. Login to comment 34 ABCC7 p.Gly542* We did not find any patients homozygous for the G542X mutation. Login to comment 35 ABCC7 p.Gly542* The haplotype of the G542X bearing chromosomes was allele 1 of T6/20-MspI, haplotype B at the D7S23 locus, allele 1 of J3.11/ MspI, allele 2 of both MetH/TaqI and MetD/ BanI, and allele 1 of MetD/TaqI. Login to comment 36 ABCC7 p.Gly551Asp ABCC7 p.Arg553* None of the other exon 11 mutations, G551D, R553X, S549 N or I, and 1717-1G-.A, was found in our patients. Login to comment 38 ABCC7 p.Gly542* Locus Met D7S23 CFTR D7S8 DNA probe MetH MetD MetD KM19 - XV2c T6/20 J3.11 Enzyme TaqI TaqI BanI PstI TaqI MspI MspI Allele haplotype 1 2 1 2 1 2 1-1 2-1 1-2 2-2 1 2 1 2 A B C D Normal chromosomes Ashkenazi (n=52) 25 24 34 4 17 33 15 8 27 2 19 3 26 25 Non-Ashkenazi (n=30) 14 9 15 7 12 17 6 4 16 4 12 3 14 16 AF508 chromosomes (n = 43) Ashkenazi (n=25) 13 4 13 0 13 5 0 22 0 3 18 0 2 21 Non-Ashkenazi (n= 18) 8 3 8 3 7 7 1 17 0 0 12 0 2 13 G542X chromosomes (n = 14) Auhrkiesho (gi (=3) 1 6 7 0 0 9 0 14 0 0 12 0 11 0 CF chromosomes, unknown mutations (n = 70) Ashkenazi (n=48) 28 2 22 1 24 6 0 43 4 1 617 3 40 Non-Ashkenazi (n=22) 11 7 15 1 12 8 1 8 9 1 7 2 7 11 Table 2 Allelic association coefficient (A)* of closely linked RFLPs and the AF508 mutation. Login to comment 47 ABCC7 p.Gly542* G542X is a termination mutation in codon 542 of the putative CFTR protein gene. Login to comment 51 ABCC7 p.Gly542* This argument is strengthened by the fact that one of the families from Turkey with G542X has the surname Ashkenazi, which was given to the Ashkenazi immigrants. Login to comment 52 ABCC7 p.Gly542* The high proportion of G542X in the patients from Turkey indicates a possible founder effect. Login to comment 53 ABCC7 p.Gly542* The haplotype ofthe G542X chromosome is unique, even when one examines the distant RFLPs at the Met and J3.11 loci. Login to comment 55 ABCC7 p.Gly542* It would be interesting to compare the haplotypes of those G542X chromosomes to those from other sources in Europe. Login to comment 56 ABCC7 p.Gly542* The mutations AF508 and G542X together account for less than 50% of the CF mutations in the Jewish patients. Login to comment 59 ABCC7 p.Trp1282* Addendum Since this manuscript was submitted we have found that the nonsense mutation, W1282X at exon 20,31' is the most frequent mutation in Ashkenazi CF chromosomes accounting for 49% (41/84) of the CF mutations. Login to comment 60 ABCC7 p.Trp1282* The W1282X mutation was found in one CF chromosome of Turkish origin and in one of North African origin. Login to comment 70 ABCC7 p.Gly542* 132 Cystic fibrosis mutations AF508 and G542X in 3rewish patients 4 Cutting GR, Kasch LM, Rosenstein BJ, et al. A cluster of cystic fibrosis mutations in the first nucleotide-binding fold of the CFTR protein. Login to comment 106 ABCC7 p.Gly542* U U KJ _// 1 6 133 #P's -d- ,Ilk, -44 I 44 .4w 0 Aw. of -40 VI* A&- Case 2 .3 16M... ........A 4 to 11%, "W... ow A Case 3 S. group.bmj.com on December 5, 2015 - Published by http://jmg.bmj.com/ Downloaded from G542X in Jewish patients. Login to comment