ABCMdb

PMID: 16980811

Kammesheidt A, Kharrazi M, Graham S, Young S, Pearl M, Dunlop C, Keiles S
Comprehensive genetic analysis of the cystic fibrosis transmembrane conductance regulator from dried blood specimens--implications for newborn screening.
Genet Med. 2006 Sep;8(9):557-62., [PubMed]

Sentences

No. Mutations Sentence Comment

73 ABCC7 p.Gly542* ABCC7 p.His199Tyr Apart from delta F508, nine other mutations were present more than once in this data set, with several mutations occurring 4-5 times (1288insTA, 2055del9insA, 406-1GϾA, G542X and H199Y). Login to comment 77 ABCC7 p.Met150Lys ABCC7 p.Tyr914* ABCC7 p.Glu257* ABCC7 p.Thr465Asn We identified eight novel CFTR mutations in seven persons in the study population (Table 2): two contained stop codons (E257X, Y914X), two were small deletions (3940delG, 2289del10ins5), two were amino acid substitutions (M150K, T465N), one was a gross deletion of exons 17A and 17B, and one was a base pair substitution (3849 ϩ 72GϾA). Login to comment 79 ABCC7 p.Thr465Asn All of the patients with novel mutations had elevated immunoreactive trypsinogen (IRT) and/or sweat tests and are clinically diagnosed with CF; however, the patient with the amino acid substitution T465N (and a known deleterious mutation at 711 ϩ 1GϾT) died in childhood and no additional clinical information is available. Login to comment 84 ABCC7 p.Tyr914* ABCC7 p.Glu257* While the interpretation of novel mutations often poses a challenge as phenotypic impact is uncertain, five of the novel mutations are likely to be deleterious: two contained stop codons (E257X, Y914X), two were small deletions (3940delG, 2289del10ins5), and one was a gross deletion of exons 17A and 17B. Login to comment 89 ABCC7 p.Met150Lys ABCC7 p.Thr465Asn The two other novel variants were amino acid substitutions(M150K,T465N).ThepatientwithM150Kalsohad the gross deletion of exons 17A and 17B. Login to comment 98 ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Arg1162* ABCC7 p.Arg1162* ABCC7 p.Arg1162* ABCC7 p.Ser1235Arg ABCC7 p.Met952Ile ABCC7 p.Ile1027Thr ABCC7 p.Gln890* ABCC7 p.Gln890* ABCC7 p.Val232Asp ABCC7 p.Val232Asp ABCC7 p.Val232Asp ABCC7 p.Arg75* ABCC7 p.Leu558Ser ABCC7 p.Ser492Phe ABCC7 p.Trp216* ABCC7 p.Trp216* ABCC7 p.Met150Lys ABCC7 p.Tyr914* ABCC7 p.Glu257* ABCC7 p.Thr465Asn ABCC7 p.Gln1100Pro In states with single specimenmodels,originalspecimensaretestedforthepresenceof themostcommonmutation,deltaF508,and/orotherdeleterious Table 1 Genotype data from panel testing and comprehensive Ambry TestTM : CF analysis Case Ethnicity ABI-31 Mutation 1 ABI-31 Mutation 2 Genzyme-87 Mutation 1 Genzyme-87 Mutation 2 Ambry Mutation 1 Ambry Mutation 2 Ambry Mutation 3 1 Hispanic delF508a 4382delAa 2 Hispanic delF508 N/I delF508 N/I delF508a 1248ϩ1GϾAa 3 African-American N/I N/I N/I N/I M150K CFTRdele17A,17Bb 4 Hispanic G542X N/I G542X N/I G542Xa 1288insTAa 5 African-American N/I N/I 3120ϩ1GϾA N/I 3120ϩ1GϾAa Q98Xa 3849؉72G>A 6 Hispanic delF508 N/I delF508 N/I delF508a 2289del10ins5a 7c Hispanic N/I N/I N/I N/I H199Ya 406-1GϾAa 8 Hispanic delF508 N/I delF508 N/I delF508a CFTRdele2,3(21kbb 9 Hispanic delF508 N/I delF508 N/I delF508a 2105-2117del13insAGAAAa 10 Hispanic G542X N/I G542X N/I G542X M952I Y914X 11 Hispanic N/I N/I N/I N/I 663delT L558S 12 Hispanic N/I N/I delF311 N/I delF311a 406-1GϾAa 13 Hispanic N/I N/I 2055del9insAa 2055del9insAa 14 Hispanic delF508 N/I delF508 N/I delF508 2055del9insA 15 Hispanic delF508 N/I delF508 N/I delF508 E257X 16 Hispanic N/I N/I N/I N/I V232D V232D 17 Hispanic delF508 N/I delF508 N/I delF508 H199Y 18 Hispanic delF508 N/I delF508 4160insGGGG 19 Caucasian delF508 N/I delF508 297-1GϾA 20 Hispanic 2183delAAϾG N/I 2183delAAϾG N/I 2183de1AAϾG 3500-2AϾG 21 Hispanic delF508 N/I delF508 S492F 22 Hispanic delF508 N/I delF508 N/I delF508 935delA 23 Caucasian R1162X N/I R1162X N/I R1162X 3940delG 24 Hispanic 711ϩ1GϾT N/I 711ϩ1GϾT T465N 25 Hispanic delF508 N/I delF508 N/I delF508 406-1GϾA 26 Hispanic delF508 N/I delF508 2055del9insA 27 Hispanic delF508 N/I delF508 N/I delF508 V232D 28 Hispanic delF508 N/I delF508 N/I delF508 S1235R 29 Hispanic G542X N/I G542X N/I G542X 297-1GϾA 30 Hispanic delF508 N/I delF508 N/I delF508 Q1100P 31 Hispanic delF508 N/I delF508 W216X 32 Hispanic N/I N/I N/I N/I 406-1GϾA H199Y 33 Hispanic N/I N/I N/I N/I 3272-26AϾG R75X 34 Hispanic N/I N/I Q890X N/I Q890X 2055del9insA 35 Hispanic delF508 N/I delF508 N/I delF508 W216X 36 Hispanic delF508 N/I delF508 N/I delF508 H199Y 37 Hispanic delF508 N/I delF508 N/I delF508 1288insTA I1027T 38 Hispanic G542X N/I G542X N/I G542X 663delT 39 Hispanic delF508 N/I delF508 N/I delF508 1288insTA 40 Hispanic delF508 N/I delF508 1288insTA mutations using mutation panels. Login to comment 110 ABCC7 p.Met150Lys ABCC7 p.Met150Lys Table 2 Clinical data of patients with novel mutations or gross deletions Case Ambry Mutation 1 Ambry Mutation 2 Ambry Mutation 3 Ethnicity Sex IRT (␮g/dL) MI Age Dxc Sweat (mEq/L) Latest Aged Height (cm) Weight (kg) 3 M150K (c.449T>A; p.M150K) CFTEdele17A,17Bb (c.2989-?_3367؉? Login to comment 111 ABCC7 p.Gly542* ABCC7 p.Arg1162* ABCC7 p.Gln98* ABCC7 p.Met952Ile ABCC7 p.Tyr914* ABCC7 p.Glu257* ABCC7 p.Glu257* ABCC7 p.Thr465Asn ABCC7 p.Thr465Asn del) AA F 572.9 No 2 mo 99 9 y 134 27 5 Q98X 3120ϩ1GϾA 3849؉72G>A (c.3717؉72G>A) AA F 253.1 No 6 mo 143 7 y 116 20 6 delF508 2289del10ins5a (c.2158_2167delACAA ATGAATinsGTAAG; p.L719fs) H M 70.8 No 1 y 104 14 y N/A N/A 8 delF508 CFTRdele2,3 (21 kb)b H F 214.2 No 3 y 103 5 y 108 18.6 10 G542X M952I Y914X (c.2742T>A;p.Y914X) H M 250.5 No 3 mo 95 6 y 112 22.2 15 delF508 E257X (c.769G>T; p.E257X) H M 301.3 No 0 mo 89 5 y N/A N/A 23 R1162X 3940delG (c.3808delG; p.D1270fs) C F N/A No 4 mo 86 8 mo 65 5.2 24 711ϩ1GϾT T465N (c.1394C>A; p.T465N) H F N/A N/A N/A N/A Deceased N/A N/A AA, African-American; H, Hispanic; C, Caucasian; MI, meconium ileus; IRT, immunoreactive trypsinogen; N/A, not available. Login to comment