title: Maternal mosaicism for a second mutational event--a novel deletion--in a familial adenomatous polyposis family harboring a new germ-line mutation in the alternatively spliced-exon 9 region of APC.
abstract: Familial Adenomatous Polyposis (FAP) is an autosomal dominant heritable disorder caused by germ-line mutations in the APC gene. To date, more than 300 germ-line mutations within this gene have been described. Using PCR, SSCP and DNA sequencing, we have identified a new mutation in the alternatively spliced region of exon 9 (1042C-->T), which results in a stop signal. This mutation manifested an aggressive form of FAP with onset of symptoms in one proband at age 17. Our results differ from reported exon 9 mutations in the spliced-out portion of the gene manifesting an attentuated form of FAP (AAPC) [Varesco et al 1994; van der Luijt et al. 1995; Curia et al. 1998; Young et al. 1998]. When analyzing this family, we encountered a mutant FAP gene which had undergone a second mutational event, a deletion. In addition to linkage analysis, both the occurrence of the two exon 9 mutation-carrier siblings, of which one is affected, harboring the same novel deletion in one generation of this family, and its absence in both parents indicates the existence of maternal germ-line mosaicism for cells bearing the latter second mutational event. Our study is only the second report of parental mosaicism in the APC gene.
authors.affiliation: Molecular Oncology Laboratory, Rambam Medical Center, Haifa, Israel.
authors.forename: Sima
authors.initials: S
authors.lastname: Davidson
authors.forename: Lucy
authors.initials: L
authors.lastname: Leshanski
authors.forename: Gad
authors.initials: G
authors.lastname: Rennert
authors.forename: Shmuel
authors.initials: S
authors.lastname: Eidelman
authors.forename: Dorit
authors.initials: D
authors.lastname: Amikam
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000235:genetics*; D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics; D000293:Adolescent; D000328:Adult; D017398:Alternative Splicing / Q000235:genetics*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D005091:Exons / Q000235:genetics*; D005260:Female; D017491:Genes, APC; D006580:Genetic Carrier Screening; D005838:Genotype; D018095:Germ-Line Mutation / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D009030:Mosaicism / Q000235:genetics*; D010375:Pedigree; D017384:Sequence Deletion
chemical_list: D025601:Adenomatous Polyposis Coli Protein; D004273:DNA, Neoplasm