Mutation in a splice-donor site of the APC gene in a family with polyposis and late age of colonic cancer death
| Autor: | G. Del Porto, Paola Sala, Viviana Gismondi, L. De Benedetti, Paola Grammatico, L. Bertario, Silvano Presciuttini, Ray White, Anna Bafico, L. Varesco, Joanna Groden, Abdelhamid Heouaine, G. B. Ferrara, C. Rossetti, Lisa Spirio |
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| Rok vydání: | 1994 |
| Předmět: |
Adult
Male Colorectal cancer Adenomatous polyposis coli RNA Splicing Molecular Sequence Data Biology Cell Line Exon APC gene Genetics medicine Humans Age of Onset Allele Child Frameshift Mutation Genetics (clinical) Aged Splice site mutation Base Sequence Autosomal dominant trait DNA Exons Middle Aged medicine.disease Exon skipping Pedigree Adenomatous Polyposis Coli biology.protein Female Age of onset |
| Zdroj: | Human Genetics. 93:281-286 |
| ISSN: | 1432-1203 0340-6717 |
| DOI: | 10.1007/bf00212023 |
| Popis: | Adenomatous polyposis coli (APC) is an autosomal dominant disease characterized by the development of hundreds of colorectal adenomatous polyps during the first decades of life. The expression of the disease varies, as the age of onset of colonic cancer and the severity of extracolonic manifestations often differ between affected families. An attenuated form of APC has also been described in which a small number of polyps and a later age of onset of colonic cancer is observed. Cloning of the APC gene has allowed disease-causing mutations in APC families to be identified. Here, we report a novel splice site mutation (a G to T transversion at position +5 of the splice donor site in intron 9) in the APC gene of affected individuals in an Italian family. Characterization of the transcription products from this mutant APC allele revealed that normal splicing was disrupted: a shorter mRNA was expressed in which exon 8 was connected directly to exon 10. This created a shift in the reading frame and the introduction of a stop codon at position 1358. In addition, some normal APC transcript was produced from the mutant allele in lymphoblastoid cells. A comparison of the clinical features of affected members of this family with four unrelated Italian APC kindreds, in which the same AAAAG deletion at position 3926 has been found, showed a significant difference in the onset of disease symptoms and in the age of death attributable to colorectal cancer. Inefficient exon skipping may be, at least in part, responsible for the delay in the development of the disease in the reported family. |
| Databáze: | OpenAIRE |
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