ABCMdb

PMID: 11668613

Wong LJ, Wang J, Zhang YH, Hsu E, Heim RA, Bowman CM, Woo MS
Improved detection of CFTR mutations in Southern California Hispanic CF patients.
Hum Mutat. 2001 Oct;18(4):296-307., [PubMed]

Sentences

No. Mutations Sentence Comment

7 ABCC7 p.Gln179Lys Eleven novel mutations were discovered in this patient group: 3876delA, 406-1G>A, 935delA, 663delT, 3271delGG, 2105-2117del13insAGAAA, 3199del6, Q179K, 2108delA, 3171delC, and 3500-2A>T. Login to comment 23 ABCC7 p.Trp1282* For example, the frequency of the W1282X mutation is about 1 to 2% in Caucasians but is as high as 60% in Ashkenazi Jews [Cystic Fibrosis Genetic Analysis Consortium, 1994; Shoshani et al., 1992]. Login to comment 80 ABCC7 p.Arg1066Cys TTGE analysis effectively detected 26 (two R1066C chromosomes were simultaneously detected by SSCP and TTGE in an earlier study) previously unidentified mutant chromosomes. Login to comment 85 ABCC7 p.Gln179Lys A total of 11 novel mutations (3876delA, 935delA, 406-1G>A, 3271delGG, 2105-2117del13insAGAAA, 663delT, 3171delC, 2108delA, Q179K, 3199del6, and 3500-2 A>T) were discovered (Table 2, indicated in bold). Login to comment 86 ABCC7 p.Gly1244Glu ABCC7 p.Gln98Arg In addition, rare mutations including1949del84, Q98R, R75X, and G1244E, were also detected. Login to comment 94 ABCC7 p.Gly542* The next most common mutations were G542X and 3849+10kbC>T, each found in five unrelated patients (4%). Login to comment 95 ABCC7 p.Gly542* These frequencies are much higher than those found in Europe and North America where G542X and 3849+10kbC>T mutations account for 2.4 and 0.2% of their patients, respectively. Login to comment 96 ABCC7 p.Arg334Trp ABCC7 p.Ile148Thr ABCC7 p.Ser549Asn ABCC7 p.Arg1066Cys Seven other mutations, I148T, S549N, R334W, 3120+1G to A, 406-1G>A, 935delA, and R1066C, occurred twice. Login to comment 110 ABCC7 p.Gln179Lys ABCC7 p.Gln179Lys The other is a 667C>A transversion that results in a nonconservative missense mutation, Q179K. Login to comment 112 ABCC7 p.Gly178Arg This is supported by the evidence that a similar mutation, a Gly to Arg change at position 178, is deleterious [Zielenski et al., 1991]. Login to comment 117 ABCC7 p.Gly551Asp ABCC7 p.Trp1282* ABCC7 p.Gly1244Glu ABCC7 p.Arg334Trp ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Arg1162* ABCC7 p.Pro205Ser ABCC7 p.Ile148Thr ABCC7 p.Gly85Glu ABCC7 p.Tyr1092* ABCC7 p.Trp1089* ABCC7 p.Arg75* ABCC7 p.Gln179Lys ABCC7 p.Gln98Arg Summary of Mutations Found in This Group of Hispanic Patients Exon or Number of Mutation intron chromosomes Frequency % Mutations detected before full gene analysis 91 73.38% 1 F508 10 64 51.6 2 G542X 11 5 4 3 3849+10kb C>T Intron 19 5 4 4 S549N 11 3 2.4 5 I148T 4 2 1.6 6 3120+1G>A 16 2 1.6 7 R334W 7 2 1.6 8 G551D 11 1 0.8 9 N1303K 21 1 0.8 10 W1282X 20 1 0.8 11 R1162X 19 1 0.8 12 G85E 3 1 0.8 13 W1089X 17b 1 0.8 14 Y1092X 17b 1 0.8 15 P205S 6a 1 0.8 Mutations detected by full gene screening 26 20.97% 16 R1066Ca 17b 2 1.6 17 1949del84 13 1 0.8 18 2184delA 13 1 0.8 19 Q98R 4 1 0.8 20 R75X 3 1 0.8 21 G1244E 20 1 0.8 22 3876delA 20 7 5.65 23 935delA 6b 2 1.6 24 406-1G>A Intron 2 2 1.6 25 3271delGG 17a 1 0.8 26 2105-2117del13insAGAAA 13 1 0.8 27 663delT 5 1 0.8 28 3171delC 17a 1 0.8 29 2108delA 13 1 0.8 30 Q179K 5 1 0.8 31 3199del6 17a 1 0.8 32 3500-2 A->T Intron 17b 1 0.8 Total identified 117 (177)b 94.35 (97.5)b Unidentified 7 (3)b 5.65 (2.5)b Total 124 (120)b 100 (100)b a This mutation was also detected by SSCP. Login to comment 122 ABCC7 p.Arg334Trp ABCC7 p.Arg1162* ABCC7 p.Ile148Thr ABCC7 p.Tyr1092* ABCC7 p.Trp1089* ABCC7 p.Arg75* ABCC7 p.Gln179Lys Clinical Presentations of Hispanic Cystic Fibrosis Patients With Novel Genotypes Patient number 1 2 3 4 5 6 7 8 9 Age/age at 7/1 (31)/0.5 23/1.2 18/9.5 (21)/15 13/0.3 18/at birth 12/7 15/0.5 diagnosisa Genotype ∆F508/3171delC W1089X/Q179K ∆F508/R75X 3271delGG/S549N I148T/3199del6 ∆F508/406-1G->A R334W/3500-2A->T 406-1G->A/unk Y1092X/R1162X Sweat Cl- 87 mEq/L (1) 79 mEq/L (0.5) 86 mEq/L (0.5) 73 mEq/L (10) 102 mEq/L (15) 100 mEq/L (0.5) 104 mEq/L (at birth) 72 mEq/L (4) 64 mEq/L (1) (age) FVC (age)b NA 59% (29) 54% (22) 75% (17) 45% (22) 81% (11); 99 (12) 60% (18) 73% (11); 71 (12) 45% (13) FEV1 (age)c NA 26% (29) 38% (22) 53% (17) 24% (22) 59% (11); 78 (12) 44% (18) 30% (11); 58 (12) 31% (13) Pancreatic Insufficient Insufficient Insufficient Insufficient Insufficient Insufficient Insufficient Insufficient Insufficient functiond Microbial Enterobacter Pseudomonas Staphylococcus Pseudomonas E. coli Staphylococcus Pseudomonas Staphylococcus Pseudomonas colonization Cloacae Aspergillus Pseudomonas Pseudomonas Staphylococcus Pseudomonas Acintobacter Aspergillus Height/weight/ 5/18/4 5/5/30 5/5/22 77/91/17 20/46/20 9/11/12 5/5/18 12/5/12 24/31/13 agee Complications Hypothyroidism RU/RML Learning Diabetes, Hypersplenism, Meconium PPD converter Chronic bronchictasis disability, depression portal ileus constipation requiring chronic hypertension, lobectomy abdominal pain liver cysts a Age and age at diagnosis are in years. Login to comment 134 ABCC7 p.Ile148Thr Patient 5 was also compound heterozygous for a missense mutation I148T. Login to comment 203 ABCC7 p.Arg1066Cys Our data show that the addition of four recurrent mutations; R1066C, 3876delA, 935delA, and 406-1G>A, increases the detection to 84%. Login to comment 210 ABCC7 p.Trp1282* ABCC7 p.Ser549Asn It also differs from that reported for Argentine patients [Chertkoff et al., 1997], where W1282X accounts for 3.1% of mutant alleles, compared to 0.8% in this study, while S549N mutation was not found in a total of 228 Argentine CF chromosomes, compared to 2.4% in our study. Login to comment