ABCMdb

PMID: 12509709

Watson MS, Desnick RJ, Grody WW, Mennuti MT, Popovich BW, Richards CS
Cystic fibrosis carrier screening: issues in implementation.
Genet Med. 2002 Nov-Dec;4(6):407-9., [PubMed]

Sentences

No. Mutations Sentence Comment

37 ABCC7 p.Arg117His The R117H mutation and its association with the 5T polymorphism was appreciated at the time the carrier screening mutation panel was developed and was discussed in some detail. Login to comment 39 ABCC7 p.Arg117His The 7T variant can also be found in CBAVD when paired with the R117H mutation. Login to comment 40 ABCC7 p.Arg117His Similarly, the 5T mutation, when paired in a trans configuration with R117H, has been found in men with CBAVD. Login to comment 41 ABCC7 p.Arg117His When R117H is paired with 5T in a cis configuration and another CF mutation is present, it is associated with a variable CF phenotype. Login to comment 44 ABCC7 p.Arg117His ABCC7 p.Arg117His Furthermore, 5T homozygosity or ⌬F508/5T has been reported in rare cases of adult-onset CF-like pulmonary disease, though on a background of TG12-M470 V that complicates its interpetation.9 However, because the goal of the screening program was to identify individuals at risk for classical CF, not CBAVD, it was recommended that 5T status only be reflexly tested or reported in a parent demonstrated to have the R117H mutation. Login to comment 52 ABCC7 p.Ile148Thr ABCC7 p.Ile148Thr Efforts continue to maintain high standards for testing laboratories as new technologies are used in CFTR mutation testing.10 I148T The I148T mutation was included in the panel on the basis of its prevalence of 0.1% in CF patients. Login to comment 54 ABCC7 p.Ile148Thr ABCC7 p.Ile148Thr At the time the panel was determined, there were one or two anecdotal reports of individuals with I148T but without CF in families in which there were individuals with CF and I148T. Login to comment 55 ABCC7 p.Ile148Thr ABCC7 p.Ile148Thr ABCC7 p.Ile148Thr After the introduction of general population carrier screening, it was observed that the I148T mutation was appearing at rates 60 to 100 times above that expected based on the rate in the CF patient population (E.M. Rohlfs, personal communication, 2002).11-14 This suggested that there was likely a modifier of the expression of I148T or that I148T was modifying the effects of another mutation. Login to comment 56 ABCC7 p.Ile148Thr Rohlfs et al.13 recently reported that I148T segregates on at least two genetic backgrounds distinguished by the 5T/7T/9T polymorphism and a CFTR deletion, 3199del6. Login to comment 57 ABCC7 p.Ile148Thr ABCC7 p.Ile148Thr ABCC7 p.Ile148Thr Among five unaffected individuals with I148T and the ⌬F508 or another I148T mutation, all had I148T on a 9T background. Login to comment 58 ABCC7 p.Asn1303Lys ABCC7 p.Ile148Thr ABCC7 p.Ile148Thr Among five individuals with CF and with ⌬F508 or N1303K mutation and I148T, four had I148T on a background of 9T and 3199del6. Login to comment 59 ABCC7 p.Ile148Thr More cases with I148T on the 3199del6 background need to studied and predictive values established. Login to comment 60 ABCC7 p.Ile148Thr In the meantime, when I148T is found in patients with CF, the haplotype background should be tested as a reflex test. Login to comment 61 ABCC7 p.Ile148Thr When found in a carrier screening program, care should be taken communicating results and laboratories should consider reflex testing to determine the genetic background on which I148T sits. Login to comment 66 ABCC7 p.Ile148Thr I148T represents an example of a genetic change that requires follow-up testing to fully understand its implications. Login to comment 100 ABCC7 p.Ile148Thr Rohlfs EM, Zhou Z, Sugarman EA, Heim RA, Pace RG, Knowles MR, Silverman LM, Allitto BA. The I148T CFTR allele occurs on multiple haplotypes: a complex allele is associated with cystic fibrosis. Login to comment