ABCMdb

PMID: 7684642

Will K, Stuhrmann M, Dean M, Schmidtke J
Alternative splicing in the first nucleotide binding fold of CFTR.
Hum Mol Genet. 1993 Mar;2(3):231-5., [PubMed]

Sentences

No. Mutations Sentence Comment

50 ABCC7 p.Arg553* X = stop mutation R553X, F = F508, N = normal. Login to comment 51 ABCC7 p.Arg553* ABCC7 p.Arg553* and dot blot analysis, we could show that the R553X carrying allele was absent in the PCR products from the R553X heterozygous probands 3, 4 and 6 (Will et al., manuscript in preparation). Login to comment 79 ABCC7 p.Arg553* In the process of analyzing the effects of the stop mutation R553X, which is located in exon 11 of the CFTR gene, we observed a new case of alternative splicing, an insertion of a 119 bp fragment between exons 10 and 11. Login to comment 80 ABCC7 p.Arg553* This additional fragment was present in three R553X heterozygous individuals. Login to comment 81 ABCC7 p.Arg553* ABCC7 p.Arg553* However, the simultaneous occurrence of R553X and the alternative splice product is probably due to a biased patient sample rather than to a influence of R553X in the splicing process. Login to comment 82 ABCC7 p.Arg553* This is supported by ourfindingthat the aberrant 119 bp fragment is present in proband 15 and in the colon carcinoma cell line T84, which both do not carry the R553X mutation (data not shown). Login to comment 95 ABCC7 p.Arg553* In both investigated families, the aberrantly spliced mRNAs were found to be transcribed from the normal alleles of the R553X heterozygous mothers. Login to comment 96 ABCC7 p.Arg553* There is no CFTR transcript detectable in the mRNA from the R553X homozygous patient, and in the second patient, alternative splicing affects the paternally derived delta F5O8 allele. Login to comment 103 ABCC7 p.Arg553* The results of our own study on transcription of the CFTR gene in patients homozygous or heterozygous for the stop mutation R553X, located in exon 11 support this observation (Will et al., manuscript in preparation). Login to comment 108 ABCC7 p.Arg553* MATERIALS AND METHODS Probands 1. CF patient, male, German origin, moderately severely affected, homozygous for the stop mutation R553X, an CGA to TGA alteration at position 1789 in exon 11, the clinical features of this patient has previously been described in greater detail (28). Login to comment 109 ABCC7 p.Arg553* ABCC7 p.Arg553* ABCC7 p.Arg553* ABCC7 p.Arg553* ABCC7 p.Arg553* 2. CF carrier (R553X), male, German origin, symptomless adult, father of 1., 3. CF carrier (R553X), female, German origin, symptomless adult, mother of 1., 4. CF patient, male, German origin, moderately severely affected, compound heterozygous for F508 and R553X, 5. CF carrier ( F508), male, German origin, symptomless adult, father of 4., 6. CF carrier (R553X), female, German origin, symptomless adult, mother of 4., 7. CF carrier (R553X), male, American origin, symptomless adult, 8. healthy female, German origin, symptomless adult, 9. healthy male, Polish origin, symptomless adult, 10. Login to comment