ABCMdb

PMID: 15507674

Hadd AG, Laosinchai-Wolf W, Novak CR, Badgett MR, Isgur LA, Goldrick M, Walkerpeach CR
Microsphere bead arrays and sequence validation of 5/7/9T genotypes for multiplex screening of cystic fibrosis polymorphisms.
J Mol Diagn. 2004 Nov;6(4):348-55., [PubMed]

Sentences

No. Mutations Sentence Comment

12 ABCC7 p.Arg117His For example, a polythymidine tract in intron 8, known as 5/7/9T, modifies the phenotype of the disease associated with the R117H polymorphism. Login to comment 13 ABCC7 p.Arg117His The R117H polymorphism is associated with either classical CF or with congenital bilateral absence of the vas deferens (CBAVD) depending on the presence and chromosome location of 5T or 7T. Login to comment 14 ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg117His The presence of 5T on the same allele (5T in cis-) with R117H is associated with classical CF; however, 7T in cis-with R117H is associated with infertility due to CBAVD in otherwise healthy men.7 The ambiguity arises when 5T is paired in a trans configuration with R117H and no other CF mutation is present, or if 5T is detected alone, because the phenotype is associated with CBAVD only.8 Testing for the R117H mutation and the intron 8 variant in a large population was recognized as a potential complication in CF screening program because it would expand the risk ascertainment beyond that for classical CF.2 Since the 5T variant alone occurs in about 5% of the US population,1 the combination of primary mutations and reflex variants in a single test can result in the detection of a 5T genotype without the R117H polymorphism. Login to comment 19 ABCC7 p.Arg117His 4, November 2004 Copyright (c) American Society for Investigative Pathology and the Association for Molecular Pathology 348 the guidelines for CF screening specify reflex testing for 5/7/9T only with the positive detection of R117H.1 However, the number of mutations and increased throughput requirements for CF screening resulted in many labs and vendors combining 5/7/9T and primary mutation panel testing in the same assay. Login to comment 33 ABCC7 p.Arg117His This approach resolved issues associated with the detection of 5T without R117H and complied with ACOG guidelines for CF reflex testing. Login to comment 197 ABCC7 p.Gly551Asp ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Ala455Glu ABCC7 p.Ala455Glu ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Arg553* ABCC7 p.Gly1349Asp ABCC7 p.Arg334Trp ABCC7 p.Arg347Pro ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Arg1162* ABCC7 p.Gln493* ABCC7 p.Val520Phe ABCC7 p.Gly85Glu ABCC7 p.Arg560Thr ABCC7 p.Phe508Cys ABCC7 p.Ile506Val Intron 8 Genotype by Coriell Number, Characterized CF Mutation and Allele Fraction for 5/7/9T Intron 8 genotype Coriell sample Characterized mutation Allele fraction by probe 5T 7T 9T 7T/7T NA09947 Normal 0.04 0.93 0.03 NA11277 ⌬I507/normal 0.06 0.90 0.04 NA11761 G551D/R553X 0.06 0.92 0.02 NA11859 2789ϩ5GϾA/2789ϩ5GϾA 0.02 0.96 0.02 NA11860 3849ϩ10kbCϾT/3849ϩ10kbCϾT 0.03 0.94 0.03 NA12444 1717-1GϾT/normal 0.06 0.87 0.07 NA12585 R1162X/normal 0.07 0.86 0.08 NA12785 R347P/G551D 0.04 0.92 0.05 NA12960 R334W/normal 0.06 0.92 0.02 NA12961 V520F/normal 0.06 0.89 0.05 NA13033 F508C/normal 0.03 0.93 0.04 9T/9T NA01531 ⌬F508/⌬F508 0.14 0.04 0.82 NA11281 621ϩ1GϾT/⌬F508 0.14 0.04 0.82 NA11283 A455E/⌬F508 0.13 0.05 0.82 NA11290 A455E/621ϩ1GϾT 0.12 0.01 0.87 NA11496 G542X/G542X 0.14 0.05 0.81 5T/7T NA11723 W1282X/normal 0.53 0.44 0.03 NA13032 I506V/normal 0.58 0.39 0.03 5T/9T NA11279 129GϾC/⌬F508 0.51 0.00 0.49 NA13591 R117H/⌬F508 0.52 0.00 0.48 7T/9T NA07441 3120ϩ1GϾA/621ϩ1GϾA 0.08 0.41 0.51 NA07552 R553X/⌬F508 0.09 0.36 0.55 NA07830 556dA/⌬F508 0.11 0.37 0.52 NA11275 3659dC/⌬F508 0.10 0.37 0.53 NA11278 Q493X/⌬F508 0.09 0.38 0.53 NA11280 711ϩ1GϾT/621ϩ1GϾA 0.09 0.37 0.54 NA11282 G85E/621ϩ1GϾA 0.07 0.39 0.53 NA11284 R560T/⌬F508 0.08 0.39 0.52 NA11472 N1303K/G1349D 0.08 0.39 0.54 Figure 3. Login to comment