ABCMdb

PMID: 7525963

Chevalier-Porst F, Bonardot AM, Gilly R, Chazalette JP, Mathieu M, Bozon D
Mutation analysis in 600 French cystic fibrosis patients.
J Med Genet. 1994 Jul;31(7):541-4., [PubMed]

Sentences

No. Mutations Sentence Comment

2 ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Asn1303Lys ABCC7 p.Gly542* The most frequent mutations in this population after AF508 (69% of the CF chromosomes) are G542X (3-3%), N1303K (1P8%), W1282X (1P5%), 1717-lG-.A (1P3%), 2184delA+2183 A-+G (0 9%), and R553X (0-8%). Login to comment 21 ABCC7 p.Arg117His ABCC7 p.Pro574His ABCC7 p.Ala455Glu ABCC7 p.Gly551Ser ABCC7 p.Gly1244Glu ABCC7 p.Arg347Leu ABCC7 p.Asn1303Lys ABCC7 p.Asp1270Asn ABCC7 p.Arg352Gln ABCC7 p.Val520Phe ABCC7 p.Ser549Arg ABCC7 p.Gly85Glu ABCC7 p.Ser549Asn ABCC7 p.Arg560Thr ABCC7 p.Arg1158* ABCC7 p.Ser549Ile ABCC7 p.Ser1255* ABCC7 p.Ser945Leu ABCC7 p.Gln552* ABCC7 p.Arg1283Met ABCC7 p.His1085Arg ABCC7 p.Gly91Arg ABCC7 p.Arg297Gln ABCC7 p.Tyr563Asn ABCC7 p.Gln890* ABCC7 p.Trp1204* ABCC7 p.Leu558Ser ABCC7 p.Gly480Cys ABCC7 p.Leu967Ser ABCC7 p.Arg560Lys ABCC7 p.Ser492Phe ABCC7 p.Thr360Lys ABCC7 p.Gln493Arg ABCC7 p.Gln1238* ABCC7 p.Cys524* ABCC7 p.Gln359Lys ABCC7 p.Ala559Thr ABCC7 p.Glu827* ABCC7 p.Phe1286Ser ABCC7 p.Tyr913Cys Among the 104 other CFTR mutations tested on the 373 non-AF508 CF chromosomes, none of the following 58 mutations were found: G91R, 435 insA, 444delA, D11OH, 556delA, 557delT, R297Q, 1154insTC, R347L, R352Q, Q359K/T360K, 1221delCT, G480C, Q493R, V520F, C524X, 1706dell7, S549R (A-C), S549N, S549I, G551S, 1784delG, Q552X, L558S, A559T, R560T, R560K, Y563N, P574H, 2307insA, 2522insC, 2556insAT, E827X, Q890X, Y913C, 2991de132 (Dork et al, personal communication), L967S, 3320ins5, 3359delCT, H1085R, R1158X, 3662delA, 3667del4, 3667ins4, 3732delA, 3737delA, W1204X, 3750delAG, I 1234V, Q1238X, 3850- 3T-+G, 3860ins31, S1255X, 3898insC, D1270N, R1283M, F1286S, 4005 + I G-A. Forty-six other mutations were found on at Distribution of CFTR mutations found in our sample ofpopulation (1200 CF chromosomes) Mutations tested No of CF chromosomes Haplotypes Method with the mutation XV2C-KM19 (% of total CF alleles) Exon 3: G85E 4 (033) 3C HinfI/ASO394delTT 2 2B PAGEExon 4: R117H 1 B ASOY122X 2 2C MseI/sequenceI148T 1 B ASO621+IG-J* 1 B MseIIASOExon 5: 711+1G--T 8(07) 8A ASOExon 7: AF311 1 C PAGE/sequencelO78delT 5 (0-42) 5C PAGE/ASOR334W 5 (0-42) 2A,2C,ID MspIlASOR347P 5 (042) 5A CfoI/NcoIR347H 1 Cfol/sequenceExon 9: A455E 1 B ASOExon 10: S492F I C DdeI/sequenceQ493X 1 D ASOl609deICA 1 C PAGE/Ddel/sequenceA1507 3 (025) 3D PAGE/ASOAF508 827 (69) 794B,30D,2C,IA PAGEl677delTA 1 A PAGE/sequenceExon I11: 1717-IG--.A 16(1-3) 14B Modified primers + AvaIIG542X 40 (3-3) 29B,5D,2A Modified primers + BstNiS549R(T--*G) 2 2B ASOG551D 3 (025) 3B HincII/Sau3AR553X 10(0-8) 6A,1B,2C,ID Hincll/sequenceExon 12: 1898+IG--A 1 C ASO1898+ IG-C 2 IC ASOExon 13: l9l8deIGC 1 A PAGE/sequence1949de184 I C PAGE/sequenceG628R(G-+A) 2 2A Sequence2118de14 I c PAGE/sequence2143de1T 1 B PAGE/modified primers2184de1A+2183A--*G 11 (0-9) lIB PAGE/ASO2184de1A 1 ASOK710X 3 (025) IC XmnI2372de18 1 B PAGE/sequenceExon 15: S945L 1 C TaqlExon 17b:L1065P I MnlIL1077P 1 A ASOY1092X 3 (025) 2C,IA Rsal/ASOExon 19: RI1162X 6 (0-5) 5C,IA DdeI/ASO3659delC 3 (025) 3C ASOExon 20: G1244E 2 2A MboIIS1251N 2 2C RsaI3905insT 4 (0-33) 4C PAGE/ASOW1282X 18 (105) 15B,1D MnlI/ASOR1283K 1 C Mnll/sequenceExon 21: N1303K 22 (1-8) 18B,lA,ID Modified primers+BstNI 47 mutations 1031 (85 9) least one CF chromosome (table): 21 of them are very rare as they were found on only one CF chromosome in our population. Login to comment 23 ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Asn1303Lys ABCC7 p.Gly542* The most frequent mutations after AF508 are G542X (33%), N1303K (1*8%), W1282X (1 5%), 1717-1G-+A (1 3%), 2184delA+ 2183A-4G (09%), and R553X (08%). Login to comment 25 ABCC7 p.Ile506Met ABCC7 p.Ile506Met IDENTIFICATION OF NEW SEQUENCE MODIFICATIONS I506M In exon 10, a C to G substitution at nucleotide position 1650 changes an isoleucine at position 506 into a methionine (I506M). Login to comment 30 ABCC7 p.Arg1283Lys R1283K When screening for W1282X5 by MnlI digestion, a patient showed a pattern similar to this mutation, except that it was on a CF chromosome bearing haplotype C (all the CF chromo- Figure 1 Heteroduplex pattern of a part of exon 10(C16B-C16D) in patients with different mutations (A) AF508/nornal. Login to comment 36 ABCC7 p.Arg1283Lys Mutation analysis in 600 French cysticfibrosis patients A A A \ T G G A A <CG G A A A C C T T G A T C Figure 2 Direct genomic sequencing of exon 20 PCR product from a heterozygous patient showing a G-+A substitution at position 3980 (R1283K). Login to comment 37 ABCC7 p.Trp1282* somes with W1282X, apart from one on haplotype D, are from haplotype B). Login to comment 38 ABCC7 p.Arg1283Lys Direct sequencing ofthe PCR product ofexon 20 from this patient showed a G to A substitution at nucleotide 3980 changing an arginine at position 1283 into a lysine (R1283K) (fig 2). Login to comment 39 ABCC7 p.Arg1283Lys It has not been established if R1283K is a disease causing mutation as the arginine at this position is not conserved in the related proteins.' Login to comment 40 ABCC7 p.Gly1244Glu ABCC7 p.Arg1283Lys R1283K can be detected by two different restriction enzyme digestions: abolition of the MnlI site or creation of an MboII site giving a pattern similar to G1244E on agarose gel electrophoresis.2' The presence of this new mutation highlights the necessity of verification by ASO hybridisation for mutations detected by abolition of a restriction enzyme site. Login to comment 41 ABCC7 p.Tyr122* We also identified four other mutations which have already been reported, a nonsense mutation in exon 4 (Y122X)22 and three frameshift mutations in exon 13, 1918delGC, 2118del4, and 2372del8.2' This study underlines some other factors. Login to comment 42 ABCC7 p.Arg334Trp ABCC7 p.Arg334Trp The identification of R334W in two affected sibs and the study of the segregation of this mutation through the family showed that the mother, without a history of CF, was homozygous for R334W. Login to comment 44 ABCC7 p.Ser1251Asn ABCC7 p.Ser1251Asn ABCC7 p.Phe508Cys ABCC7 p.Phe508Cys This mutation has previously been described as a "mild" mutation.24 As reported by Kalin et al,25 the two CF chromosomes (from unrelated patients) positive for S1251N also carry the polymorphism F508C,26 but two other CF chromosomes bearing F508C are negative for S1251N and have unknown mutations. Login to comment 47 ABCC7 p.Trp1282* In our study, W1282X has a higher frequency than in the rest of France (CFGAC). Login to comment 57 ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Asn1303Lys ABCC7 p.Gly542* For the other partner, who has an initial risk of being a carrier of 1 in 25, the screening ofthe seven mutations AF508, G542X, N1303K, W1282X, 1717-1G-+A, 2184delA+2183A-.G, and R553X allows a better estimation ofthis risk; it drops to 1 in 120 if this screening is negative. Login to comment 82 ABCC7 p.Arg347His ABCC7 p.Arg352Gln ABCC7 p.Glu585* Four new mutations of the CFTR gene (541delC, R347H, R352Q, E585X) detected by DGGE analysis in Italian CF patients, associated with different clinical phenotypes. Login to comment 99 ABCC7 p.Ala120Thr ABCC7 p.Gln30* 15 Chillon M, Casals T, Gimenez J, Nunes V, Estivill X. Analysis of the CFTR gene in the Spanish population: SSCP screening for 60 known mutations and identification of four new mutations (Q30X, A120T, 1812-1G-+A and 3667del4. Login to comment 130 ABCC7 p.Trp1282* 28 Shoshani T, Augarten A, Gazit E, et al. Association of a nonsense mutation (W1282X), the most common mutation in the Ashkenazi Jewish cystic fibrosis patients in Israel, with presentation of severe disease. Login to comment 132 ABCC7 p.Arg553* 29 Liechti-Gallati S, Bonsall I, Malik N, et al. Genotype/ phenotype association in cystic fibrosis: analyses of the AF508, R553X, and 3905insT mutations. Login to comment