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
| Autor: | Dorit Amikam, Lucy Leshanski, Sima Davidson, Gad Rennert, Shmuel Eidelman |
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| Rok vydání: | 2001 |
| Předmět: |
Proband
Adult Male Genes APC Adolescent Genotype Mutant Adenomatous Polyposis Coli Protein DNA Mutational Analysis Biology medicine.disease_cause Familial adenomatous polyposis Exon Germline mutation Genetics medicine Humans Gene Genetics (clinical) Germ-Line Mutation Sequence Deletion Mutation Mosaicism Genetic Carrier Screening Alternative splicing DNA Neoplasm Exons medicine.disease Molecular biology Pedigree Alternative Splicing Adenomatous Polyposis Coli Haplotypes Female |
| Zdroj: | Human mutation. 19(1) |
| ISSN: | 1098-1004 |
| Popis: | 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 (1042CT), 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. © 2001 Wiley-Liss, Inc. |
| Databáze: | OpenAIRE |
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