Analysis of CFTR transcripts in nasal epithelial cells and lymphoblasts of a cystic fibrosis patient with 621 + 1G-->T and 711 + 1G-->T mutations.
| Autoři: | Zielenski J; Department of Genetics, Hospital for Sick Children, Toronto, Ontario, Canada., Bozon D, Markiewicz D, Aubin G, Simard F, Rommens JM, Tsui LC |
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| Zdroj: | Human molecular genetics [Hum Mol Genet] 1993 Jun; Vol. 2 (6), pp. 683-7. |
| Způsob vydávání: | Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
| Jazyk: | English |
| Informace o časopise: | Publisher: IRL Press at Oxford University Press Country of Publication: England NLM ID: 9208958 Publication Model: Print Cited Medium: Print ISSN: 0964-6906 (Print) Linking ISSN: 09646906 NLM ISO Abbreviation: Hum Mol Genet Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Oxford, England ; New York : IRL Press at Oxford University Press, c1992- |
| Výrazy ze slovníku MeSH: | RNA Splicing*, Cystic Fibrosis/*genetics , Membrane Proteins/*genetics , RNA, Messenger/*genetics, Alleles ; B-Lymphocytes/metabolism ; Base Sequence ; Cell Line, Transformed ; Cells, Cultured ; Cystic Fibrosis/blood ; Cystic Fibrosis/pathology ; Cystic Fibrosis Transmembrane Conductance Regulator ; Epithelium/pathology ; Exons ; Herpesvirus 4, Human ; Heterozygote ; Membrane Proteins/biosynthesis ; Molecular Sequence Data ; Nasal Mucosa/pathology ; Nasal Polyps/genetics ; Nasal Polyps/pathology ; Open Reading Frames ; Polymerase Chain Reaction ; RNA, Neoplasm/genetics ; Sequence Deletion ; Transcription, Genetic |
| Abstrakt: | We have analyzed the CFTR mRNA populations in a cystic fibrosis patient heterozygous for the 621 + 1G-->T and 711 + 1G-->T mutations. Total RNA isolated from the nasal epithelial cells and Epstein-Barr virus-transformed lymphoblasts derived from this patient was reversely transcribed and a region extending from exon 3 to exon 7 of the gene was amplified by the polymerase chain reaction and analyzed. Three abnormal products were identified, suggesting the presence of three aberrant transcripts, and their profiles were identical in both cell types. Two of the products were found to be missing either exon 4 or exon 5 as anticipated from the transcripts from the 621 + 1G-->T or 711 + 1G-->T alleles, respectively. The third product was apparently derived from an alternatively spliced mRNA species in the absence of the nominal splice site (in 621 + 1G-->T) through the use of a cryptic splice donor sequence (TT528/GTGAGG) within exon 4. Although reading frames appeared to be preserved in all three putative transcripts, significant portions of the presumed first and second transmembrane spans as well as the immediately following cytoplasmic domain would be deleted from the mutant CFTR polypeptides, if made. These observations are consistent with a loss of CFTR function in this cystic fibrosis patient. |
| Grant Information: | DK34944-8 United States DK NIDDK NIH HHS |
| Gene Symbol: | CFTR |
| Substance Nomenclature: | 0 (Membrane Proteins) 0 (RNA, Messenger) 0 (RNA, Neoplasm) 126880-72-6 (Cystic Fibrosis Transmembrane Conductance Regulator) |
| Entry Date(s): | Date Created: 19930601 Date Completed: 19930921 Latest Revision: 20190512 |
| Update Code: | 20231215 |
| DOI: | 10.1093/hmg/2.6.683 |
| PMID: | 7689008 |
| Autor: | Zielenski J; Department of Genetics, Hospital for Sick Children, Toronto, Ontario, Canada., Bozon D, Markiewicz D, Aubin G, Simard F, Rommens JM, Tsui LC |
| Jazyk: | angličtina |
| Zdroj: | Human molecular genetics [Hum Mol Genet] 1993 Jun; Vol. 2 (6), pp. 683-7. |
| DOI: | 10.1093/hmg/2.6.683 |
| Abstrakt: | We have analyzed the CFTR mRNA populations in a cystic fibrosis patient heterozygous for the 621 + 1G-->T and 711 + 1G-->T mutations. Total RNA isolated from the nasal epithelial cells and Epstein-Barr virus-transformed lymphoblasts derived from this patient was reversely transcribed and a region extending from exon 3 to exon 7 of the gene was amplified by the polymerase chain reaction and analyzed. Three abnormal products were identified, suggesting the presence of three aberrant transcripts, and their profiles were identical in both cell types. Two of the products were found to be missing either exon 4 or exon 5 as anticipated from the transcripts from the 621 + 1G-->T or 711 + 1G-->T alleles, respectively. The third product was apparently derived from an alternatively spliced mRNA species in the absence of the nominal splice site (in 621 + 1G-->T) through the use of a cryptic splice donor sequence (TT528/GTGAGG) within exon 4. Although reading frames appeared to be preserved in all three putative transcripts, significant portions of the presumed first and second transmembrane spans as well as the immediately following cytoplasmic domain would be deleted from the mutant CFTR polypeptides, if made. These observations are consistent with a loss of CFTR function in this cystic fibrosis patient. |
| Databáze: | MEDLINE |
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