ABCMdb

PMID: 12394352

Richards CS, Bradley LA, Amos J, Allitto B, Grody WW, Maddalena A, McGinnis MJ, Prior TW, Popovich BW, Watson MS, Palomaki GE
Standards and guidelines for CFTR mutation testing.
Genet Med. 2002 Sep-Oct;4(5):379-91., [PubMed]

Sentences

No. Mutations Sentence Comment

50 ABCC7 p.Trp1282* ABCC7 p.Asn1303Lys ABCC7 p.Gly542* Depending upon the ethnic group, these mutation frequencies may be difficult to obtain (Table 1).5-7 CF 2.8.1 The most common mutations in the Ashkenazi Jewish population have been described.8-10 These include W1282X, ⌬F508, G542X, N1303K, and 3849 ϩ 10 kbCϾT. Login to comment 51 ABCC7 p.Ser549Arg ABCC7 p.Asp1152His ABCC7 p.Trp1089* A recent report by Orgad et al.11 indicated that additional mutations were found in Jewish Israeli populations, including D1152H, 405 ϩ 1GϾA, W1089X, and S549R. Login to comment 52 ABCC7 p.Gly480Cys ABCC7 p.Gly330* ABCC7 p.Ala559Thr CF 2.8.2 Mutations specific for the African-American population have been described12 and include 3120 ϩ 1GϾA, A559T, G330X, 2307insA, ⌬F311, and G480C. Login to comment 57 ABCC7 p.Asp1270Asn ABCC7 p.Ser549Asn ABCC7 p.Trp1089* Mutations not included in the 25 mutation core testing panel that have been reported in these populations include D1270N, W1089X, and S549N.13-15 CF 2.8.4 Insufficient information is available for the Asian American population. Login to comment 60 ABCC7 p.Arg117His ABCC7 p.Ala455Glu ABCC7 p.Arg334Trp ABCC7 p.Gly85Glu Examples of such mutations include R117H, 3849 ϩ 10 kbCϾT, A455E, 2789 ϩ 5GϾA, G85E, and R334W. Login to comment 87 ABCC7 p.Arg117His ABCC7 p.Ile148Thr For example, R117H and I148T mutations may produce a more variable clinical phenotype, depending upon genetic modifiers, some of which may not be well defined. Login to comment 181 ABCC7 p.Phe508Cys It is critical that laboratories include known variants in the mutation panel to prevent mistyping of compound genotypes such as F508C/⌬F508. Login to comment 217 ABCC7 p.Phe508Cys ABCC7 p.Phe508Cys As for ASO typing, it is critical to include frequent polymorphisms in the coding region of the CFTR gene, e.g., F508C, to prevent mistypings of polymorphism/mutant compound heterozygous genotypes such as F508C/⌬F508. Login to comment 218 ABCC7 p.Arg117His As described below, it is desirable to determine the 5/7/9T genotype only for diagnostic cases or carriers positive for the R117H mutation. Login to comment 307 ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg117His 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.Ile148Thr ABCC7 p.Gly85Glu ABCC7 p.Arg560Thr ⌬F508 R553X R1162X 2184delA 3120ϩ1GϾA ⌬I507 G542X G551D W1282X N1303K 621ϩ1GϾT R117H 1717-1GϾA A455E R560T G85E R334W R347P 711ϩ1GϾT 1898ϩ1GϾA 1078delT 3849ϩ10kbCϾT 2789ϩ5GϾA 3659delC I148T CF 3.3.2 Inclusion of the common R117H mutation in the test panel screens for CBAVD as well as for CF: The phenotypic consequences of the R117H mutation are modulated in cis by the 5/7/9T polypyrimidine tract in intron 8 such that R117H/7T is associated with CBAVD and R117H/5T is associated with CF.34 Moreover, the 5T allele is associated as a trans mutation in CBAVD.35 It is recommended that the 5/7/9T variant be excluded from the routine carrier screen but tested as a reflex for carriers shown to be heterozygous for the R117H mutation. Login to comment 308 ABCC7 p.Arg117His The 5/7/9T variant should be included for diagnostic panels to distinguish the genotypes of R117H associated with CF from those associated with CBAVD and as a potential pathogenic mutation for CBAVD. Login to comment 311 ABCC7 p.Phe508Cys For example, I506 V and F508C are performed as reflex tests for ⌬F508 positives unless it is proven that these variants do not cause assay interference. Login to comment 342 ABCC7 p.Arg117His ABCC7 p.Arg117His CF 3.5.2 Comments on phenotype issues with CBAVD, R117H and 5T, 7T background: ACMG has recommended that all R117H positive results require reflex testing for the 5T/7T/9T variant in the polythymidine tract at intron 8 in CFTR gene. Login to comment 343 ABCC7 p.Arg117His ABCC7 p.Arg117His Refer to model reports for carrier screening presented in the ACMG statement.1 For R117H/5T positive heterozygotes, testing of parents is recommended to determine the inheritance of the R117H and the 5T variant (i.e., cis vs. trans position). Login to comment 344 ABCC7 p.Arg117His ABCC7 p.Arg117His If the R117H and 5T variant are determined to be in cis, then the report should reflect that this mutation has been associated with a variable phenotype when R117H/5T (cis) or another CFTR mutation is present in patients with CF. Login to comment 345 ABCC7 p.Arg117His If the R117H mutation and 5T are determined to be in trans, the report should indicate that the individual carries a relatively benign CF mutation that is not generally associated with the phenotype of typical CF patients but has been associated with CBAVD, leading to infertility in males and no known clinical features in females. Login to comment 348 ABCC7 p.Arg117His ABCC7 p.Arg117His For individuals who are R117H positive and 5T negative, the report should indicate that the R117H mutation is not expected to lead to a typical CF clinical phenotype. Login to comment 349 ABCC7 p.Arg117His However, R117H has been associated with CBAVD. Login to comment