![]() ![]() ![]() Familial Adenomatous Polyposis: Desmoid Tumours and Lack of Ophthalmic Lesions (CHRPE) Associated with APC Mutations beyond Codon 1444. doi: 10.1016/j.critrevonc.2006.07.004.Ĭaspari R., Olschwang S., Friedl W., Mandl M., Boisson C., Böker T., Augustin A., Kadmon M., Möslein G., Thomas G. Correlations between Mutation Site in APC and Phenotype of Familial Adenomatous Polyposis (FAP): A Review of the Literature. Hereditary Colorectal Polyposis and Cancer Syndromes: A Primer on Diagnosis and Management. Kanth P., Grimmett J., Champine M., Burt R., Samadder N.J. Molecular Origins of Cancer: Molecular Basis of Colorectal Cancer. Right: Sequencing electropherograms of the RT-PCR products obtained. Center: Schematic diagrams showing the RT-PCR products obtained. Left: Agarose gel electrophoresis showing the RT-PCR products obtained with the SD6 and SA2 primers from HEK-293 cells transfected with the pSP元 empty vector (263 bp), the pSP元 vector with the genomic APC fragment from the wild type allele (341 bp), or the pSP元 vector with the genomic APC fragment from the mutant allele (263 bp), and untransfected HEK-293 cells (negative control). ( B) RT-PCR analysis of transcripts derived from the indicated pSP元 reporter minigenes transfected in HEK-293 cells. EcoRI and BamHI indicate the cloning sites used to subclone the genomic APC fragments obtained from the wild type and mutant alleles (c.1621_1626+7del). The pSP元 vector contains two exons (SD and SA) and a functional intron, with transcription beginning after the SV40 promoter and ending at the late poly(A) signal (LPAS). ( A) Schematic representation of the pSP元 minigene reporter used for the molecular characterization of APC splicing mutation c.1621_1626+7del. Splicing minigene reporter assay based on the pSP元 exon-trapping vector. The APC splicing mutations causing skipping of exon 12 or 13 considered in this study cluster with the AFAP phenotype and reveal a potential molecular mechanism of pathogenesis in FAP disease.ĪPC FAP pathogenesis exon skipping familial adenomatous polyposis splicing. Among these, only a small proportion (9/69) results in an in-frame protein, with four mutations causing skipping of exon 12 or 13 with loss of armadillo repeat 2 (ARM2) and 3 (ARM3), and five mutations leading to skipping of exon 5, 7, 8, or (partially) 9 with loss of regions not encompassing known functional domains. ![]() We found that 119 unique APC splicing mutations, including the one described here, have been reported in FAP patients, 69 of which have been characterized at the mRNA level. Moreover, we performed a literature meta-analysis of APC splicing mutations. Here, we characterized a novel germline heterozygous splice donor site mutation in APC exon 12 (NM_000038.5: c.1621_1626+7del) leading to exon 12 skipping in an Italian family with the attenuated FAP (AFAP) phenotype. Mutations leading to aberrant APC splicing have rarely been reported. To date, nearly 2000 APC mutations have been described in FAP, most of which are predicted to result in truncated protein products. Familial adenomatous polyposis (FAP) is caused by germline mutations in the tumor suppressor gene APC. ![]()
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