ABCMdb

PMID: 10649490

Girodon-Boulandet E, Cazeneuve C, Goossens M
Screening practices for mutations in the CFTR gene ABCC7.
Hum Mutat. 2000;15(2):135-49., [PubMed]

Sentences

No. Mutations Sentence Comment

58 ABCC7 p.Tyr1092* HA and REA are both very simple and rapid, and are thus suitable for a number of situations such as prenatal diagnosis, testing for known mutations in at-risk relatives, and testing for mutations frequent in particular ethnic groups (for instance 394delTT in Northern Europe, Y1092X in Eastern Europe and 1811+1.6kbA>G in Spain). Login to comment 63 ABCC7 p.Gly551Asp ABCC7 p.Gly551Asp ABCC7 p.Arg553* nate between ∆F508 and ∆I507; and 2) G551D and R553X could not be distinguished when exon 11 was cut with Hinc II (although Mbo I digestion can be used to test for the corresponding restriction site introduced by G551D). Login to comment 74 ABCC7 p.Arg1066Cys ABCC7 p.Tyr1092* ABCC7 p.Asp1152His ABCC7 p.Arg668Cys ABCC7 p.Asp443Tyr However, it still fails to cover several mutations frequent in certain geographical areas, such as 394delTT, 405+1G>A, 2143delT, 1677delTA, Y1092X, R1066C, 3272- 26A>G and 1811+1.6kbA>G, and other mutations frequent in CBAVD patients, such as IVS8-5T, D443Y, R668C and D1152H. Login to comment 81 ABCC7 p.Phe508Cys ABCC7 p.Arg1162Leu For example, an allele bearing the 1655T/G (F508C) polymorphism may not be recognized when using F508- or∆F508- specific probes in hybridization-based methods; with the PE Biosystems OLA kit, the presence of the 3617G/T (R1162L) polymorphism prevents ligation with the normal R1162 and mutated X1162 probes, while a∆F508 homozygous signal may correspond to∆F508 / 1716G/A (E528E) compound heterozygosity, as the 3' primer for PCR of exon 10 includes the 3' end of this exon. Login to comment 92 ABCC7 p.Asn1303Lys One limitation of the DGGE technique is that homozygous mutations that do not change the stability of DNA fragments (e.g., N1303K and 3659delC) may be missed. Login to comment 175 ABCC7 p.Arg117His For instance, the R117H mutation, for which most commercial kits test, is now considered to be a CF mutation only when it is associated in ciswith the IVS8-5T variant or when sweat test or nasal potential difference values are abnormal [Rosenstein and Cutting, 1998]. Login to comment 176 ABCC7 p.Arg117His This would imply that laboratories should routinely analyse the IVS8-6 polyvariant site once R117H has been detected, which is especially important for genetic counseling of the patients themselves and their relatives. Login to comment 178 ABCC7 p.Arg75Gln ABCC7 p.Leu997Phe Likewise, other missense mutations which have been considered as non CF alleles on the basis on linkage studies could be moderately deleterious and/or worsen the effect of a CF mutation in a CF patient, or be responsible for a mild phenotype when combined intrans with a CF mutation, as suggested for R75Q (356G/ A) [Oates and Amos, 1993], E528E (1716G/A) [Cuppens and Cassiman, 1995], and L997F (3123G/C) [Pignatti et al., 1995; Girodon et al., 1997]. Login to comment 179 ABCC7 p.Asp1270Asn ABCC7 p.Asp1270Asn ABCC7 p.Arg74Trp ABCC7 p.Arg74Trp The functional consequence of the double mutant R74W-D1270N was recently studied [Fanen et al., 1999]: R74W was shown to be a polymorphism with regard to chloride channel function, but was found to aggravate the deleterious effect of D1270N. Login to comment 180 ABCC7 p.Asp1270Asn ABCC7 p.Asp1270Asn ABCC7 p.Arg74Trp D1270N alone is thus considered as a CBAVD mutation, while R74W-D1270N is considered as a CF mutation, in keeping with a previous clinical observation [Casals et al., 1995]. Login to comment