ABCMdb

PMID: 10571949

Lazaro C, de Cid R, Sunyer J, Soriano J, Gimenez J, Alvarez M, Casals T, Anto JM, Estivill X
Missense mutations in the cystic fibrosis gene in adult patients with asthma.
Hum Mutat. 1999;14(6):510-9., [PubMed]

Sentences

No. Mutations Sentence Comment

57 ABCC7 p.Gly542* TheCFTR gene was analyzed for the two most common mutations in the Spanish population (∆F508 and G542X) and for a DNA variant located in intron 8 of the CFTR gene, IVS8-6(5T) [Chu et al., 1991]. Login to comment 61 ABCC7 p.Arg75Gln ABCC7 p.Arg668Cys ABCC7 p.Gly576Ala ABCC7 p.Leu997Phe Missense mutations R75Q, G576A, and L997F were analyzed in the extended sample of individuals from the general population by conventional restriction analysis; mutation R668C was analyzed by SSCA. Login to comment 71 ABCC7 p.Arg1066Cys Among the15 differentmissensemutationsiden- tified in the patients with asthma, only mutation R1066C is relatively common in Spanish CF patients (~1%), while the other mutations were either not found in a sample of over 700 unrelated Spanish CF patients or have relative frequencies of less than 0.1% in this population [Casals et al., 1997]. Login to comment 72 ABCC7 p.Thr896Ile ABCC7 p.Val855Ile ABCC7 p.Ala534Gln ABCC7 p.Met1028Arg Five new missense mutations (A534Q, V855I,T896I,M1028R,andT1142I)weredetected in this study for the first time (Table 2). Login to comment 73 ABCC7 p.Arg668Cys ABCC7 p.Gly576Ala Among the six subjects with two CFTR mutations (Table 1), three presented mutations R668C and G576A. Login to comment 75 ABCC7 p.Arg668Cys ABCC7 p.Gly576Ala However, some studies have detected that mutations R668C and G576A are associated on the same chromosome [Dörk et al., 1997] and it is likely that they correspond to the same CFTR allele. Login to comment 76 ABCC7 p.Leu997Phe Moreover, one patient was homozygous and two were heterozygous for L997F, a mutation previously detected in patients with CF-PS, DB, and CBAVD. Login to comment 77 ABCC7 p.Arg75Gln ABCC7 p.Arg668Cys ABCC7 p.Gly576Ala ABCC7 p.Leu997Phe Overall, four of the 15 missense mutations (R75Q, G576A, R668C, and L997F) were detected in 57% of the 21 asthma patients. Login to comment 79 ABCC7 p.Arg75Gln ABCC7 p.Arg668Cys ABCC7 p.Gly576Ala ABCC7 p.Leu997Phe With the exception of mutation L997F (2.1% in asthma patients), which was not found in control group 2, the other three mutations were found in these samples with the following frequencies: R75Q (1.6% general population individuals vs. 2.8% asthma patients); G576A (2.7% general population individuals vs. 2.1% asthma patients) and R668C (4.3% general population individuals vs. 3.5% asthma patients). Login to comment 84 ABCC7 p.Arg74Trp ABCC7 p.Ile148Thr ABCC7 p.Arg75Gln ABCC7 p.Arg75Gln ABCC7 p.Arg75Gln ABCC7 p.Arg75Gln ABCC7 p.Arg1066Cys ABCC7 p.Arg668Cys ABCC7 p.Arg668Cys ABCC7 p.Arg668Cys ABCC7 p.Arg668Cys ABCC7 p.Arg668Cys ABCC7 p.Gly576Ala ABCC7 p.Gly576Ala ABCC7 p.Gly576Ala ABCC7 p.Leu997Phe ABCC7 p.Leu997Phe ABCC7 p.Leu997Phe ABCC7 p.Leu997Phe ABCC7 p.Thr896Ile ABCC7 p.Thr582Arg ABCC7 p.Thr1220Ile ABCC7 p.Ala534Gln ABCC7 p.Met1028Arg ABCC7 p.Thr1142Ile Characteristics of Asthmatic Patients With CFTR Mutations CFTR Age IgE Skin Patients genotype1 M470V2 PolyT3 Sex Years BHR4 IU/ml5 test6 SB221 R74W,V8551 M/V 7/7 M 67 - 329 + SB36 R75Q / - M/V 7/7 F 61 + 59 + SB47 R75Q / - M/V 7/9 M 67 NA 42 NA SB131 R75Q / - M/V 7/7 F 69 + 41 - SB296 R75Q / - M/V 7/9 F 45 + 96 - SB251 I148T / - M/V 7/9 F 70 - 25 - SB212 A534Q / - M/M 7/7 F 46 + 69 + SB125 R668C,G576A N/V 7/7 M 62 + 21 - SB154 R668C,G576A M/V 7/7 M 65 + 93 + SB231 R668C,G576A M/V 7/7 F 45 + 158 + SB112 R668C / - M/V 7/7 M 64 + 1350 + SB304 R668C,T582R M/V 7/7 F 78 - 7 - SB56 T896I / - M/V 7/7 M 72 + 77 - SB117 L997F / - V/V 7/9 F 81 NA 6 NA SB143 L997F/L997F V/V 7/7 F 39 NA 129 NA SB173 L997F / - M/V 7/9 F 67 + 127 - SB148 M1028R / - M/V 7/7 F 48 + 23 - SB32 R1066C / - M/V 7/7 F 69 - 9 - SB69 T1142I / - M/M 7/9 M 65 - 158 + SB92 R116L / - M/V 7/7 M 78 NA 64 NA SB53 T1220I / - M/M 7/9 F 60 + 62 + SB40 ∆F508 / - M/M 79 F 62 + 34 + SB9 - / - M/M 5/9 F 61 - 169 - SB20 - / - M/V 5/5 F 57 - 245 + SB116 - / - V/V 5/7 F 33 NA 41 NA SB118 - / - M/V 5/9 M 83 + 63 - SB140 - / - V/V 5/7 F 72 NA 35 NA SB142 - / - M/V 5/7 F 59 + 108 + SB201 - / - M/V 5/7 M 27 - 297 + SB205 - / - M/V 5/7 F 56 - 20 - SB284 - / - M/V 5/7 F 71 - 40 NA SB316 - / - M/V 5/7 F 78 NA 20 - 1 The CFTR genotype was studied by DGGE/SSCP analysis of all CFTR exons and intronic flanking sequences. Login to comment 93 ABCC7 p.Arg1162* ABCC7 p.Arg74Trp ABCC7 p.Ile148Thr ABCC7 p.Arg75Gln ABCC7 p.Arg1066Leu ABCC7 p.Arg668Cys ABCC7 p.Gly576Ala ABCC7 p.Leu997Phe ABCC7 p.Arg1162Leu ABCC7 p.Arg75* ABCC7 p.Arg1066His ABCC7 p.Thr896Ile ABCC7 p.Arg1066Ser ABCC7 p.Gly576* ABCC7 p.Met1028Ile ABCC7 p.Ala534Glu ABCC7 p.Thr582Arg ABCC7 p.Thr1220Ile ABCC7 p.Val855Ile ABCC7 p.Thr582Ile ABCC7 p.Ile148Asn ABCC7 p.Ala534Gln ABCC7 p.Met1028Arg ABCC7 p.Thr1142Ile ABCC7 p.Arg75Leu Characteristics of 15 Amino Acid Variants/Mutants in the CFTR Gene Detected in 21 Patients With Asthma Other Evolutive Conservative Other mutations Mutation1 Reference2 Exon Domain3 Patients4 phenotypes5 conservation6 change7 at same position R74W Claustres et al., 1993 3 IC1 1 CF-PS/CBAVD b, m, r, s NC - R75Q Zielenski et al., 1991 3 IC2 4 CF-PS/DB/CBAVD/ b, d, m, r, s, x NC R75X (CF) CF Parents R75L (CBAVD) I148T Bozon et al., 1994 4 IC2 1 CF-PS b, d, m, r, s, x NC I148N (CF) A534Q This report 11 NBF1 1 - b, m NC A534E (CF) G576A Fanen et al., 1992 12 NBF1 3 CF-PS/CBAVD b, m, r, s NC G576X (CF) T582R Casals et al., 1997 12 NBF1 1 CF-PS b, d, m, r, s, x NC T582I (CF) R668C Fanen et al., 1992 13 R 5 DB/CF-PS/CBAVD/ b, d, m, r, s, x NC - CF Parents V855I This report 14a IC6 1 - b, r, s C - T896I This report 15 EC4 1 - b, d, m, r, s NC - L997F Fanen et al., 1992 17a TM9 3 DB/CF-PS/CBAVD/ b, d, m, r, s, x C - non-CF M1028R This report 17a TM10 1 - d NC M1028I (CF) T2066C Fanen et al., 1992 17b IC8 1 DB/CF-PI b, d, m, r, s, x NC R1066S (CF) R1066L (CF) R1066H (CF/CBAVD) T1142I This report 18 TM12 1 - b, d, m, r, s, x NC - R1162L Fanen et al., 1992 19 IC9 1 non-CF b, d, m, r, s, x NC R1162X (CF) T1220I Ghanem et al., 1994 19 NBF2 1 DB/non-CF b, d NC - 1 Mutation name according to the Cystic Fibrosis Genetic Analysis Consortium. Login to comment 114 ABCC7 p.Leu997Phe ABCC7 p.Val855Ile Most (87%) of the mutations detected here are nonconservative amino acid substitutions, with the exception of V855I and L997F. Login to comment