ABCMdb

PMID: 15371902

Watson MS, Cutting GR, Desnick RJ, Driscoll DA, Klinger K, Mennuti M, Palomaki GE, Popovich BW, Pratt VM, Rohlfs EM, Strom CM, Richards CS, Witt DR, Grody WW
Cystic fibrosis population carrier screening: 2004 revision of American College of Medical Genetics mutation panel.
Genet Med. 2004 Sep-Oct;6(5):387-91., [PubMed]

Sentences

No. Mutations Sentence Comment

54 ABCC7 p.Ile148Thr ABCC7 p.Ile148Thr The mutation/variant I148T occurs at rates 50 to 100 times higher than in the general population being tested for carrier status than in patients.8,9 It was shown that CFTR genes bearing I148T in CF patients have a second mutation termed 3199del6. Login to comment 55 ABCC7 p.Ile148Thr The vast majority of individuals in the general population with I148T do not have the 3199del6 mutation. Login to comment 57 ABCC7 p.Ile148Thr ABCC7 p.Ile148Thr ABCC7 p.Ile148Thr ABCC7 p.Ile148Thr ABCC7 p.Ile148Thr ABCC7 p.Ile148Thr One, CF patients have been described who lack I148T but have 3199del6 in association with another CF causing mutation.10 Two, unaffected individuals have been described who have a CF mutation associated with severe CF and I148T but lacking 3199del6.7-11 Because the frequency of I148T alone is 0.05% and I148T with 3199del6 in this analysis is considerably lower than 0.1% and because I148T does not cause classical CF by itself, we recommend removing I148T from the CF carrier screening panel. Login to comment 61 ABCC7 p.Arg117His Furthermore, individuals with R117H and 5T are at risk of having offspring with CF if their partner is also a CF carrier and should be counseled accordingly. Login to comment 63 ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg117His Because the frequency of R117H-5T is appreciable, the Working Group recommends retaining R117H, whereas emphasizing the need to perform a screening test for 5T only as a reflex when R117H is present. Login to comment 65 ABCC7 p.Arg117His Warner et al.12 suggest that it is inappropriate to screen for mutations such as R117H for which a definitive prediction of clinical outcome can not be provided. Login to comment 70 ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Ala455Glu ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Arg334Trp ABCC7 p.Arg347Pro ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Arg1162* ABCC7 p.Gly85Glu ABCC7 p.Arg560Thr It has been ar- Table 1 CFTR mutation frequency among individuals with clinically diagnosed cystic fibrosis by racial/ethnic group and in a pan-ethnic U.S. population CFTR mutation Mutation frequency among individuals with clinically diagnosed cystic fibrosis (%) Non-Hispanic Caucasian Hispanic Caucasian African American Asian American Ashkenazi Jewish Pan-Ethnic Population5 delF508 72.42 54.38 44.07 38.95 31.41 66.31 G542X 2.28 5.10 1.45 0.00 7.55 2.64 W1282X 1.50 0.63 0.24 0.00 45.92 2.20 G551D 2.25 0.56 1.21 3.15 0.22 1.93 621ϩ1GϾT 1.57 0.26 1.11 0.00 0.00 1.30 N1303K 1.27 1.66 0.35 0.76 2.78 1.27 R553X 0.87 2.81 2.32 0.76 0.00 1.21 dell507 0.88 0.68 1.87 0.00 0.22 0.90 3849ϩ10kbCϾT 0.58 1.57 0.17 5.31 4.77 0.85 3120ϩ1GϾT 0.08 0.16 9.57 0.00 0.10 0.86 R117H 0.70 0.11 0.06 0.00 0.00 0.54 1717-1GϾT 0.48 0.27 0.37 0.00 0.67 0.44 2789ϩ5GϾA 0.48 0.16 0.00 0.00 0.10 0.38 R347P 0.45 0.16 0.06 0.00 0.00 0.36 711ϩ1GϾT 0.43 0.23 0.00 0.00 0.10 0.35 R334W 0.14 1.78 0.49 0.00 0.00 0.37 R560T 0.38 0.00 0.17 0.00 0.00 0.30 R1162X 0.23 0.58 0.66 0.00 0.00 0.30 3569delC 0.34 0.13 0.06 0.00 0.00 0.28 A455E 0.34 0.05 0.00 0.00 0.00 0.26 G85E 0.29 0.23 0.12 0.00 0.00 0.26 2184delA 0.17 0.16 0.05 0.00 0.10 0.15 1898ϩ1GϾA 0.16 0.05 0.06 0.00 0.10 0.13 l148T 0.09 0.09 0.05 0.00 0.10 0.08 1078delT 0.02 0.09 0.00 0.00 0.00 0.03 Total 88.40 71.90 64.51 48.93 94.14 84.00 gued that a laboratory is obligated to report any and all information that is gleaned from a test system, however, there is no regulatory requirement and practice varies. Login to comment 71 ABCC7 p.Arg117His Because the CF mutation testing platforms included the reflex tests this led to the reporting of the 5T allele in the absence of R117H by some laboratories. Login to comment 79 ABCC7 p.Ile148Thr Recent experience with I148T serves to demonstrate the importance of evaluating distribution among both affected and carrier screening populations to discern discrepancies before inclusion in a screening panel. Login to comment