ABCMdb

PMID: 9108869

Warren WS, Hamosh A, Egan M, Rosenstein BJ
False-positive results of genetic testing in cystic fibrosis.
J Pediatr. 1997 Apr;130(4):658-60., [PubMed]

Sentences

No. Mutations Sentence Comment

26 ABCC7 p.Phe508Cys Because of the discrepancy between the results of mutation analysis and the patient's clinical course and sweat electrolyte concentrations, direct sequencing of CFTRexon 10 was carried out with polymerase chain reaction-amplified genomic DNA.3This revefiled compound heterozygosity for AF508 and F508C (Figure), a polymorphism not known to be associated with clinical disease. Login to comment 27 ABCC7 p.Phe508Cys Because of the discrepancy between the results of mutation analysis and the patient's clinical course and sweat electrolyte concentrations, direct sequencing of CFTRexon 10 was carried out with polymerase chain reaction-amplified genomic DNA.3This revefiled compound heterozygosity for AF508 and F508C (Figure), a polymorphism not known to be associated with clinical disease. Login to comment 29 ABCC7 p.Phe508Cys Vertical lines, WT sequenceat codon508;angle brackets, deletionoftheTTC,whichcausesthe AF508mutation;arrow, T---~G transversion,which causes the F508C mutation. Login to comment 30 ABCC7 p.Phe508Cys Vertical lines, WT sequenceat codon508;angle brackets, deletionoftheTTC,whichcausesthe AF508mutation;arrow, T---~G transversion,which causes the F508C mutation. Login to comment 31 ABCC7 p.Phe508Cys CFTR beating the AF508 mutation results in a nonfunctional protein.4 The F508C mutation in compound heterozygosity with AF508 has been previously reported in six subjects.6-1&#b0;Five were completely free of symptoms, and one had isolated congenital absence of the vas deferens without other stigmata of CF. Login to comment 32 ABCC7 p.Phe508Cys CFTR beating the AF508 mutation results in a nonfunctional protein.4 The F508C mutation in compound heterozygosity with AF508 has been previously reported in six subjects.6-1°Five were completely free of symptoms, and one had isolated congenital absence of the vas deferens without other stigmata of CF. Login to comment 33 ABCC7 p.Ser1251Asn ABCC7 p.Phe508Cys Two German patients with CF were found to carry AF508 on one allele and both F508C and the S1251N mutation on the other allele.11 Several states and districts screen newborn infants for CF because of its high incidence.l'~Screening programs use an assay for rRT, a pancreatic enzyme precursor that is persistently elevated in the blood of infants with CF. Login to comment 34 ABCC7 p.Ser1251Asn ABCC7 p.Phe508Cys Two German patients with CF were found to carry AF508 on one allele and both F508C and the S1251N mutation on the other allele.11 Several states and districts screen newborn infants for CF because of its high incidence.l'~Screening programs use an assay for rRT, a pancreatic enzyme precursor that is persistently elevated in the blood of infants with CF. Login to comment 39 ABCC7 p.Phe508Cys However, the other allele could not hybridize with the AF508 oligonucleotidebecause it does not contain that sequence, or with the normal oligonucleotide because the T--+G transversion, which gives rise to the F508C polymorphism, prevents hybridization to that sequence. Login to comment 40 ABCC7 p.Phe508Cys However, the other allele could not hybridize with the AF508 oligonucleotidebecause it does not contain that sequence, or with the normal oligonucleotide because the T--+G transversion, which gives rise to the F508C polymorphism, prevents hybridization to that sequence. Login to comment 42 ABCC7 p.Phe508Cys ABCC7 p.Phe508Cys This problem was reported previously in a fetus at 25% risk of AF508 homozygosity Who was found to be a AF508/F508C compound heterozygote afterreverse dot blot testing ofhis healthy father showed homozygosity for AF508.1&#b0; Sequencing of genomic DNA from both the father and the fetus revealed the compound heterozygosity for AF508/F508C. Login to comment 43 ABCC7 p.Phe508Cys ABCC7 p.Phe508Cys This problem was reported previously in a fetus at 25% risk of AF508 homozygosity Who was found to be a AF508/F508C compound heterozygote afterreverse dot blot testing ofhis healthy father showed homozygosity for AF508.1° Sequencing of genomic DNA from both the father and the fetus revealed the compound heterozygosity for AF508/F508C. Login to comment 49 ABCC7 p.Phe508Cys ABCC7 p.Phe508Cys Third, the use of allele-specific oligonucleotide analysis, whether by dot blot or reverse dot blot analysis, will lead to false-positive results in patients who are compound heterozygotes for AF508 and F508C until an oligonucleotide designed to detect the F508C mutation is added to dot blot and reverse dot blot schemes of mutation detection, as has been done by some DNA diagnostic laboratories. Login to comment 50 ABCC7 p.Phe508Cys ABCC7 p.Phe508Cys Third, the use of allele-specific oligonucleotide analysis, whether by dot blot or reverse dot blot analysis, will lead to false-positive results in patients who are compound heterozygotes for AF508 and F508C until an oligonucleotide designed to detect the F508C mutation is added to dot blot and reverse dot blot schemes of mutation detection, as has been done by some DNA diagnostic laboratories. Login to comment