ABCMdb

PMID: 10746558

Bombieri C, Giorgi S, Carles S, de Cid R, Belpinati F, Tandoi C, Pallares-Ruiz N, Lazaro C, Ciminelli BM, Romey MC, Casals T, Pompei F, Gandini G, Claustres M, Estivill X, Pignatti PF, Modiano G
A new approach for identifying non-pathogenic mutations. An analysis of the cystic fibrosis transmembrane regulator gene in normal individuals.
Hum Genet. 2000 Feb;106(2):172-8., [PubMed]

Sentences

No. Mutations Sentence Comment

6 ABCC7 p.Leu1096Arg ABCC7 p.Ile1131Val Four new mutations were identified: 1341+28 C/T, 2082 C/T, L1096R, and I1131V. Login to comment 74 ABCC7 p.Leu1096Arg ABCC7 p.Ile1131Val These findings include four novel mutations described here for the first time: 1341+28 C/T, 2082 C/T, L1096R, and I1131V. Login to comment 79 ABCC7 p.Asn1303Lys ABCC7 p.Ile148Thr ABCC7 p.Gly85Glu ABCC7 p.Arg75Gln ABCC7 p.Ser1235Arg ABCC7 p.Phe1052Val ABCC7 p.Val562Leu ABCC7 p.Arg668Cys ABCC7 p.Gly576Ala ABCC7 p.Arg31Cys ABCC7 p.Lys68Glu ABCC7 p.Leu997Phe Out of the 20 missense mutations, three (G85E, ∆F508, and N1303K) are certainly CF-causing, and several (R31C, K68E, R75Q, I148T, V562L, G576A-R668C, L997F, F1052V, S1235R) have been described in congenital bilateral absence of the vas deferens, in disseminated bronchiectasis, in pancreatitis, or in atypical CF cases mutations as reported in the CFGAC website (). Login to comment 80 ABCC7 p.Asn1303Lys ABCC7 p.Ile148Thr ABCC7 p.Gly85Glu ABCC7 p.Arg75Gln ABCC7 p.Ser1235Arg ABCC7 p.Phe1052Val ABCC7 p.Val562Leu ABCC7 p.Gly622Asp ABCC7 p.Leu1096Arg ABCC7 p.Arg668Cys ABCC7 p.Gly576Ala ABCC7 p.Arg31Cys ABCC7 p.Ile506Val ABCC7 p.Ile1131Val ABCC7 p.Leu997Phe ABCC7 p.Ile1027Thr ABCC7 p.Arg1162Leu ABCC7 p.Arg170His Many (13 out of 20) of the missense mutations change highly conserved (5/5 species analyzed) amino acid residues (R75Q, G85E, I148T, I506V, R668C, G622D, L997F, I1027T, F1052V, L1096R, I1131V, R1162L, N1303K); others affect amino acid residues conserved in 4/5 species (K68 E, R170H, M470V, V562L, S1235R), or in 3/5 species (R31C and G576A; Tucker et al. 1992). Login to comment 86 ABCC7 p.Arg668Cys ABCC7 p.Gly576Ala In addition to very common mutations, which are often associated with other mutations in the same gene, two sporadic mutations were found together in the same individual (G576A and R668C once; 3041-71 G/C and 4002 A/G twice) in three cases. Login to comment 88 ABCC7 p.Asn1303Lys ABCC7 p.Ser1235Arg ABCC7 p.Phe1052Val ABCC7 p.Ile1027Thr In three further cases where more than one sporadic mutation was observed in the same individual (1341+28 C/T and F1052V and S1235R; ∆F508 and I1027T; 1716G/A and N1303K), data from the literature were not available, and segregation analysis was not possible; thus, their phase could not be established. Login to comment 91 ABCC7 p.Asn1303Lys ABCC7 p.Gly85Glu The remaining 30 (after having excluded the certainly CF-causing mutations G85E, ∆F508 and N1303K) have been found a few times only: once (20 mutations), twice (five mutations), three times (three mutations), four times (one mutation), and eight times (one mutation). Login to comment 96 ABCC7 p.Ile148Thr ABCC7 p.Arg75Gln ABCC7 p.Ser1235Arg ABCC7 p.Phe1052Val ABCC7 p.Val562Leu ABCC7 p.Gly622Asp ABCC7 p.Leu1096Arg ABCC7 p.Arg668Cys ABCC7 p.Gly576Ala ABCC7 p.Arg31Cys ABCC7 p.Ile506Val ABCC7 p.Ile1131Val ABCC7 p.Lys68Glu ABCC7 p.Leu997Phe ABCC7 p.Ile1027Thr ABCC7 p.Arg1162Leu ABCC7 p.Arg170His Moreover, 1525-61 A/G (i 9) and 3601-65 C/A (i 18) were detected by SSCA performed in the Spanish sample only (14/82 and 12/80, respectively); these mutations were not identifiable by DGGE as used in the present work The totals are: a378; b362; c380; d356 genes eCertainly a CF-causing mutations fThe most common allele at this site is (TTGA)7 gThe most common allele at this site is T7 hThe frequency shown is that of the M allele Mutation Position North-Central Southern Spain Total East Italy Italy France 82 genes 100 genes 100 genes 100 genes 382 genes % 125 G/C 5`UTR 1 2 7 3 13 3.4 R31C 2 1 1 1 0 3 0.8 K68E 3 1 0 0 0 1 0.3 R75Q 3 1 1 2 0 4 1.0 G85Ee 3 0 1 0 0 1 0.3 406-6 T/C i 3 0 0 1 0 1 0.3 I148T 4 1 0 0 0 1 0.3 621+3 A/G i 4 0 1 0 0 1 0.3 R170H 5 1 0 0 0 1 0.3 875+40 A/G i 6a 11 5 5 2 23 6.0 (TTGA)6 f i 6a 17 11 7 13 48 12.6 1341+28 C/T i 8 1 0 0 0 1 0.3 IVS8-6g T5 i 8 8 2 4 3/78 17a 4.5 IVS8-6g T9 i 8 10 7 10 11/78 38a 10.0 M470Vh 10 42 30 39 27 138 36.1 I506V 10 1 0 0 0 1 0.3 ∆F508e 10 1 0 2 0 3 0.8 1716 G/A 10 2 1 0 5 8 2.1 V562L 12 0 0 1 0 1 0.3 G576A 12 1 0/80 1 0 2b 0.6 G622D 13 0 0/80 1 0 1b 0.3 R668C 13 1 0/80 1 0 2b 0.6 2082 C/T 13 1 0/80 0 0 1b 0.3 2377 C/T 13 0 0/80 0 1 1b 0.3 2694 T/G i 14a 33 23 33 14/80 103c 27.1 2752-15 C/G i 14b 0 3 0 0 3 0.8 3041-71 G/C i 15 0 1 2 0 3 0.8 L997F 17a 0 2 0 0 2 0.5 I1027T 17a 1 0 0 0 1 0.3 F1052V 17b 1 0 0 0 1 0.3 L1096R 17b 0 0 1 0 1 0.3 3417 A/T 17b 1 0 1 0 2 0.5 I1131V 18 0 1 0 0 1 0.3 R1162L 19 0 1 0 0 1 0.3 3690 A/G 19 0 0 0 1/80 1c 0.3 S1235R 19 1 0 0 0 1 0.3 4002 A/G 20 2 3 3 3/80 11c 2.9 4005+28insA i 20 0 1 0 0 0.3 4029 A/G 21 1 0 0 0 1 0.3 N1303Ke 21 1 0 0 0 1 0.3 4404 C/T 24 1 0 1 0 2 0.5 4521 G/A 24 21 16 14/80 15/76 66d 18.5 Total 165 113 137 98 513 encountered in the present survey are possible. Login to comment 115 ABCC7 p.Arg75Gln ABCC7 p.Arg668Cys ABCC7 p.Gly576Ala ABCC7 p.Arg31Cys ABCC7 p.Leu997Phe The density of polymorphic sites, which is essentially the proportion of sites susceptible to evolving among the total number of sites (bp) of that gene, can be estimated by counting the number n of polymorphic sites existing in 177 Table 4 A list of the 13 ED-C mutations detected in this survey Mutation q±SE q-2.5SE 125 G/C 0.0340±0.0093 0.011 875+40 A/G 0.0602±0.0122 0.030 876-5 (GATT)6 0.1257±0.0170 0.083 IVS8 T5 0.0450±0.0107 0.018 IVS8 T9 0.1005±0.0155 0.062 IVS8 (TG)10 0.2900±0.0262 0.223 IVS8 (TG)12 0.0867±0.0162 0.046 1525-61 A/Ga 0.1750±0.0420 0.070 M470V 0.3613±0.0246 0.300 2694 T/G 0.2711±0.0228 0.214 3601-65 C/Aa 0.1500±0.0399 0.050 4002 A/G 0.0289±0.0086 0.007 4521 G/A 0.1854±0.0206 0.134 aSearched by SSCA in the sample of 40 Spanish individuals only: frequency and standard error are those of that sample Table 5 Distribution in the four subsamples of mutations found a few times but not classified Total number of Subsample times the mutation has been found NE Italy Central Southern Spain Italy France Twice G576A 1 - 1 - R668C 1 - 1 - L997F - 2 - - 3417 A/T 1 - 1 - 4404 C/T 1 - 1 - Three times R31C 1 1 1 - 2752-15 C/G - 3 - - 3041-71 G/C - 1 - Four times R75Q 1 1 2 - Eight times 1716 G/Aa 2 1 - 5 aGiven its frequency and distribution, this mutant will probably turn out to be a C mutant the stretch under study of N bp and dividing n by N. Usually, the number of sites identified as polymorphic sites is merely a minimum estimate of the total number n of polymorphic sites of the N stretch, because the number of polymorphic sites of the stretch that escaped detection remains unknown. Login to comment