RESUMEN
BACKGROUND: The estimated ratio of hereditary breast/ovarian cancer (HBOC) based on family history is 1.5% in Latvia. This is significantly lower than the European average of 5-10%. Molecular markers like mutations and SNPs can help distinguish HBOC patients in the sporadic breast and ovarian cancer group. METHODS: 50 patients diagnosed with HBOC in the Latvian Cancer Registry from January 2005 to December 2008 were screened for BRCA1 founder mutation-negatives and subjected to targeted resequencing of BRCA1 and BRCA2 genes. The newly found mutations were screened for in the breast and ovarian cancer group of 1075 patients by Real Time-PCR/HRM analysis and RFLP. RESULTS: Four BRCA2 mutations including three novel BRCA2 frameshift mutations and one previously known BRCA2 frameshift mutation and one BRCA1 splicing mutation were identified. Two of the BRCA2 mutations were found in a group of consecutive breast cancer patients with a frequency of 0.51% and 0.38%. CONCLUSIONS: Molecular screening of sequential cancer patients is an important tool to identify HBOC families.
Asunto(s)
Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias de la Mama/genética , Detección Precoz del Cáncer , Neoplasias Ováricas/genética , Secuencia de Bases , Neoplasias de la Mama/diagnóstico , Femenino , Efecto Fundador , Mutación del Sistema de Lectura , Genes BRCA1 , Genes BRCA2 , Predisposición Genética a la Enfermedad , Humanos , Letonia , Neoplasias Ováricas/diagnóstico , Linaje , Análisis de Secuencia de ADNRESUMEN
OBJECTIVE: To determine the prevalence and clinical significance of human parvovirus B19 (B19) infection in patients with rheumatoid arthritis (RA). METHODS: One hundred patients with RA and 94 apparently healthy blood donor controls were enrolled for study. Plasma samples of patients and controls were examined for the presence of anti-B19-specific antibodies by ELISA. B19 DNA was detected in plasma and peripheral blood leukocyte (PBL) samples of all patients and controls as well as in synovial fluid cells of 38 RA patients by nested polymerase chain reaction. Disease activity and clinical manifestations were determined in RA patients with and without markers of B19 infection. RESULTS: IgM anti-B19-specific antibodies were detected in 24.0% of RA patients; B19 DNA was found in plasma and/or PBL, synovial fluid cells in 34.0% (34 patients); in 14.0% of the cases (14 patients) both markers were found. In blood donor controls, anti-B19 IgM antibodies were observed in 16.0% (15 donors) and B19 DNA in 6.4% (6 donors); all donors with detectable B19 genomic DNA were IgM-positive. The disease activity in patients with and without B19 infection was similar, while the frequency of clinical complications was significantly higher in the patients with anti-B19 IgM antibodies. Moreover, liver failure and sicca syndrome were observed in the viremic patients only. CONCLUSION: Our study confirms observations regarding a high prevalence of B19 DNA in patients with RA, and a possible role of this viral infection in the pathogenesis of RA.