ABCMdb

PMID: 7691344

Claustres M, Laussel M, Desgeorges M, Giansily M, Culard JF, Razakatsara G, Demaille J
Analysis of the 27 exons and flanking regions of the cystic fibrosis gene: 40 different mutations account for 91.2% of the mutant alleles in southern France.
Hum Mol Genet. 1993 Aug;2(8):1209-13., [PubMed]

Sentences

No. Mutations Sentence Comment

20 ABCC7 p.Arg74Trp R74W. Login to comment 26 ABCC7 p.Gly551Asp ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Arg334Trp ABCC7 p.Arg347Pro ABCC7 p.Arg347His ABCC7 p.Gly542* ABCC7 p.Arg1162* ABCC7 p.Asp1270Asn ABCC7 p.Arg74Trp ABCC7 p.Ile148Thr ABCC7 p.Glu585* ABCC7 p.Leu206Trp ABCC7 p.Gly85Glu ABCC7 p.Ser549Asn ABCC7 p.Tyr122* ABCC7 p.Pro67Leu ABCC7 p.Arg1158* ABCC7 p.Arg792* ABCC7 p.Tyr1092* ABCC7 p.Ser945Leu ABCC7 p.Lys710* Mutations identified in a Southern french population mutation AF5O8 M1K 300delA P67L R74W G85E 394detTT 406-6 (T-C) Y122X I148T 621 + 1G-T 62/+2T-G L206W 1078deIT R334W R347H R347P AI507 1717-1G-A G542X R553X S549N G551D E585X 2184delA K710X R792X S945L Y1092X 3272-26A-G R1158X R1162X 3737delA 3659delC 11234V D1270N W1282X N13O3H N13O3K 4382delA Exon 10 1 3 3 3 3 3 intron 3 4 4 intron 4 intron 4 6a 7 7 7 7 10 intron 10 11 11 11 11 , 12 13 13 13 15 17b intron 17a 19 19 19 19 19 20 20 21 21 24 Amino acid change 3 bp deletion start-Lys at 1 frameshift Pro-Leu at67 Arg-Trp at 74 Gly-Glu at 85 frameshift splice mutation? Login to comment 38 ABCC7 p.Leu206Trp L206W. Login to comment 41 ABCC7 p.Arg792* R792X. Login to comment 43 ABCC7 p.Ser945Leu S945L. Login to comment 53 ABCC7 p.Arg74Trp SSCP aft Sequence Sequence I l-CT A C G T - -T 405+46 (G or T) R74W Figure 2. Login to comment 54 ABCC7 p.Arg74Trp SSCP and sequence analysis of 309-bp PCR fragments containing exon 3 in a CF patient carrying both the possible mutation R74W and the rare variation 405 +46 (G or T). Login to comment 55 ABCC7 p.Arg74Trp The black symbol indicates the presence of R74W, inherited from the mother, while a hatched half symbol indicates the presence of an unknown mutation inherited from the father. Login to comment 59 ABCC7 p.Arg74Trp Previously undescribed polymorphisms Two rare variants have been identified in one CF patient each: 405+46 (G or T) in intron 3, which destroys a Nsil site and was found on the chromosome carrying the mutation R74W (Figure 2), and 3726 (G or T) in exon 19 that does not change PAGE Sequence G T 300delA 394delTT 394delTT Figure 3. Characterization of a 2-bp deletion in exon 3: 394delTT. Login to comment 66 ABCC7 p.Leu206Trp The (gatt)^ repeats in intron 6a were found associated to L206W in the three unrelated patients carrying this mutation (Figure 5). Login to comment 67 ABCC7 p.Arg792* The patient with the mutation R792X has also a T-to-C transition in exon 15, that was first reported to the CF Consortium as a possible missense mutation. Login to comment 68 ABCC7 p.Arg792* ABCC7 p.Leu967Ser As the stop mutation R792X in exon 13 is a causing disease mutation that leads in a premature termination of the protein product, the rare sequence alteration first named 'L967S' in exon 15 should rather be considered as a polymorphism 3032 T or C. DISCUSSION The SSCP approach for detecting the CFTR mutations has been found reliable and effective in this study, as we characterized 91.2% of mutations responsible for CF in a small area from Southern France. Login to comment 72 ABCC7 p.Leu206Trp ABCC7 p.Leu206Trp As the sensitivity of SSCP in detecting point Sequence -T-G SSCP SSCP <*M L206W L206W Sequence (gatt) repeats intron 6a 6x 7x 8x / 6x 7x / 6x 7x / 7x intron 6a (gatt) repeats Figure 5. Login to comment 73 ABCC7 p.Leu206Trp Single stranded conformatkmal and sequence analysis of both the mutation L206W in exon 6a and the sequence repeat (gatt) immediately preceding exon 6b. Login to comment 74 ABCC7 p.Leu206Trp The familial segregations of L206W together with the (gatt) 8x repeats are shown in two unrelated pedigrees. Login to comment 75 ABCC7 p.Leu206Trp The SSCP analysis of L206W has been performed on 385-bp PCR fragments; the (gatt) repeats have been analyzed after digestion of PCR fragments containing exon 6b by Ddel. Login to comment 83 ABCC7 p.Arg792* Single strand conformation polymorphism (SSCP) analysis 100 ng ofgenormc DNA from each individual was amplified by poh/merase chain reaction (PCR) using each of the 27 sets of primers described by Zielenski a al (22), except for exon 1, that was screened by denaturing gradient gel SSCP Sequence C-T- R792X Figure 6. Login to comment 84 ABCC7 p.Arg792* Identification of the stop mutation R792X in exon 13 (the size of PCR products analyzed by SSCP is 497-bp). Login to comment 95 ABCC7 p.Ser945Leu SSCP SSCP Seance C-T- 3032 T or C A T G T S945L T-C- \ C G T Sequence Figure 7. Login to comment 97 ABCC7 p.Ser945Leu Left, identification of mutation S945L and familial segregation analyzed by SSCP (after digestion of PCR fragments by Taql). Login to comment