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DGH - Posters/abstracts em congressos nacionais

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Browsing DGH - Posters/abstracts em congressos nacionais by Author "Albuquerque, Cristina"

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  • The MSH2 exon 5 deletion (c.792+8_943-450del) is a founder mutation in Portuguese Lynch syndrome families with a Center-South ancestry
    Publication . Francisco, Inês; Claro, I.; Lage, P.; Ferreira, S.; Rosa, I.; Rodrigues, P.; Theisen, Periera; Pereira-Caetano, Iris; van der Klift, H.; Tops, C.; Gonçalves, João; Dias Pereira, A.; Albuquerque, Cristina
    Introduction: Lynch syndrome (LS) is a hereditary colorectal cancer syndrome caused by germline mutations in the DNA mismatch repair (MMR) genes. Worldwide, large genomic deletions, particularly in MSH2 gene, account for ~20% of the mutational spectrum. The aim of this study was to evaluate a possible founder effect of a recurrent exon 5 deletion in MSH2 gene, detected in 10% of the families from the LS family registry of the Portuguese Oncology Institute in Lisbon. This mutation was not reported by other Portuguese Oncology Centers and it was described only once in the literature, in a family with Portuguese ancestry [1]. Methods: We analyzed 15 unrelated LS families (11 from our registry, 3 from INSA and one family from LUMC) with the MSH2 exon 5 deletion, detected by MLPA, including a total of 57 individuals (30 carriers and 27 non-carriers, all samples were anonymized). The genomic breakpoint was identified by direct sequencing and haplotype analysis was performed using 6 microsatellite markers flanking MSH2 (from D2S2174 to D2S123, spanning ~6Mb) and three intragenic SNPs. Results: All families shared the same deletion breakpoints (c.792+8_943-450del) and a common haplotype, extending from D2S391 to D2S2227 microsatellite marker (0.858 Mb). Considering the average of mutation and recombination events in this region, we estimate that this mutation occurred ~400 years ago. Discussion: Our data suggests that the MSH2 exon 5 deletion (c.792+8_943-450del) is a founder mutation in Portugal, which is reinforced by the fact that, for seven families, it has been possible already to establish a common geographical origin. Moreover, the high frequency of the exon 5 deletion in our LS registry indicates that screening of this mutation, using MLPA, should be considered a first and cost-effective approach in the genetic diagnosis of suspected LS families with a Portuguese ancestry, especially in those with a Center-South origin. [1] – Soravia et al., Am J Med Genet A. 2003
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