Browsing by Author "Rodrigues, P."
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- Distinct spectrum of apc germline mutations in familial adenomatous polyposis at the center-south of portugal: identification of a mutational hotspot and suggestion of a founder effectPublication . Filipe, B.; Claro, I.; Lage, P.; Ferreira, S.; Rosa, I.; Rodrigues, P.; Spier, I.; Theisen, Patrícia; Pereira-Caetano, Iris; Isidro, Glória; Gonçalves, João; Aretz, S.; Dias Pereira, A.; Albuquerque, C.Introduction: Familial adenomatous polyposis (FAP) is caused by APC germline mutations. These have been reported in classic and attenuated FAP (AFAP) but only two hotspots were described (codons 1309 and 1061-range:0-15%). We aimed to characterize the APC mutation spectrum in a FAP/AFAP population from the familial polyposis registry of the Portuguese Oncology Institute in Lisbon. Methods: We performed mutation analysis in 95 index patients from our FAP/AFAP cohort (61 FAP; 34 AFAP) using PTT, DGGE, sequencing and MLPA. Haplotype analysis was performed using 3 microsatellite markers flanking APC and 2 intragenic SNPs in 12 families with an intron 9 mutation (6 from our registry, 2 from INSA and 4 from IHG), occasionally detected in the literature, in order to evaluate a possible founder effect. All samples were anonymized. Statistics: Fisher’s exact and Χ2. Results: APC mutations were found in 47/61(77%) FAP and in 12/34(35%) AFAP families. The 1309del and 1061del contributed for 6/59(10%) and 2/59(4%) of the families, respectively. Exon 15 mutations were more frequent in FAP than in AFAP [30/47(64%) vs 1/12(8%),P<0.001]. A high mutation frequency was also found in exon 9 and flanking regions (9/59;15%), contributing for the majority of AFAP with APC mutation (8/12;67%). An intron 9 mutation (c.1312+3A>G) was highly represented (6/59,10%), exclusively in AFAP (6/12;50%). Segregating with this mutation, we detected a common haplotype apparently shared by 6 families. For D5S346, the common allele segregating with this haplotype was more frequent in the index patients (11/20;46%) than in a control population (20/90;22%). Discussion: We identified a specific distribution of APC mutations and a mutational hotspot in our population. The higher frequency of the c.1312+3A>G mutation in Center-South Portugal suggest a non-uniform distribution which may be explained by a founder effect. Further studies using SNPs flanking intron 9 and the analysis of more families/relatives are needed.
- The MSH2 exon 5 deletion (c.792+8_943-450del) is a founder mutation in Portuguese Lynch syndrome families with a Center-South ancestryPublication . 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, CristinaIntroduction: 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
- Ticks on passerines from the Archipelago of the Azores as hosts of borreliae and rickettsiaePublication . Literak, I.; Norte, A.C.; Núncio, M.S.; Lopes de Carvalho, I.; Ogrzwalska, M.; Novákvá, M.; Martins, T.F.; Sychra, O.; Resendes, R.; Rodrigues, P.We examined the presence of borreliae and rickettsiae bacteria in ticks from wild passerine birds on three islands of the Archipelago of the Azores, the westernmost region of Palearctic. A total of 266 birds belonging to eight species from seven families were examined on São Miguel, Santa Maria and Graciosa islands in 2013. Ticks collected from these birds consisted of 55 Ixodes frontalis (22 larvae, 32 nymphs, 1 adult female) and 16 Haemaphysalis punctata nymphs. Turdus merula and Erithacus rubecula were the birds most infested with both tick species. Three T. merula in Santa Maria were infested with 4 I. frontalis infected with Borrelia turdi. No rickettsiae were found in the ticks.We reportfor the firsttime the presence of I. frontalis and B. turdi on the Azores islands and we showed that the spatial distribution reaches further west than previously thought.