ABCMdb

PMID: 19893581

Forzan M, Salviati L, Pertegato V, Casarin A, Bruson A, Trevisson E, Di Gianantonio E, Clementi M
Is CFTR 621+3 A>G a cystic fibrosis causing mutation?
J Hum Genet. 2010 Jan;55(1):23-6. Epub 2009 Nov 6., [PubMed]

Sentences

No. Mutations Sentence Comment

6 ABCC7 p.Gln552* Third, we have identified an asymptomatic individual who harbored the 621+3 A4G variant in trans with the Q552X mutation. Login to comment 11 ABCC7 p.Ile148Thr An example is the I148T variant initially reported as a CF mutation, which is now considered a non-pathogenic nucleotide change.3 We have chosen to study the 621+3 A4G nucleotide change because one of us had tested positive for this variant during a CFscreening program. Login to comment 48 ABCC7 p.Gln552* Patient data In the course of the study we identified by chance an individual who harbored the 621 +3A4G variant in trans with the pathogenic Q552X-truncating mutation. Login to comment 53 ABCC7 p.Gln552* She was identified to be the carrier of both alterations because her parents underwent CF screening during a second pregnancy: the mother was found to harbor 621+3 A4G, whereas the father had tested positive for Q552X. Login to comment 92 ABCC7 p.Ile148Thr However, this technique cannot detect heterozygous deletions of individual exons, that may be present in up to 60% of classic CF patients in whom a single-point mutation is detected.20 This case is similar to that of the I148T variant, which by itself is not a CF disease-causing mutation, but in some patients it is found in cis with the 3199del6 mutation.21 Extensive analysis of CFTR, including gene rearrangements, should be performed in all patients with typical CF symptoms harboring the 621+3 A4G allele, to identify a possible other mutation in cis with this variant, which could account for the severe phenotype. Login to comment 93 ABCC7 p.Gln552* In conclusion, our data suggest that 621+3 A4G should not be considered a severe CF mutation because of its frequency in the population, because it still allows the synthesis of significant amounts of functional CFTR protein, and the absence of clinical disease in a compound (621+3 A4G/ Q552X) heterozygote individual. Login to comment 101 ABCC7 p.Asp1270Asn ABCC7 p.Arg74Trp ABCC7 p.Ile148Thr 3 Claustres, M., Altieri, J. P., Guittard, C., Templin, C., Chevalier-Porst, F. & Des Georges, M. Are p.I148T, p.R74W and p.D1270N cystic fibrosis causing mutations? Login to comment 103 ABCC7 p.Asp565Gly ABCC7 p.Glu822* 4 Tzetis, M., Efthymiadou, A., Doudounakis, S. & Kanavakis, E. Qualitative and quantitative analysis of mRNA associated with four putative splicing mutations (621+3A4G, 2751+2T-4A, 296+1G-4C, 1717-9T-4C-D565G) and one nonsense mutation (E822X) in the CFTR gene. Login to comment 139 ABCC7 p.Ile148Thr 21 Monaghan, K. G., Highsmith, W. E., Amos, J., Pratt, V. M., Roa, B., Friez, M. et al. Genotype-phenotype correlation and frequency of the 3199del6 cystic fibrosis mutation among I148T carriers: results from a collaborative study. Login to comment