BRCA1 5272-1G>A and BRCA2 5374delTATG are founder mutations of high relevance for genetic counselling in breast/ovarian cancer families of Spanish origin.

The distribution of BRCA1 and BRCA2 germ line mutations in breast/ovarian cancer families varies among different populations, which typically present a wide spectrum of unique mutations. Splicing mutation 5272-1G>A of BRCA1 and frameshift mutation 5374delTATG of BRCA2 are highly prevalent mutations in Castilla-León (Spain), accounting for 18.4% and 13.6% of BRCA1 and BRCA2 positive families, respectively. To test the presence of founder effects, 9 Spanish 5272-1G>A and 13 5374delTATG families were genotyped with polymorphic markers linked to BRCA1 or BRCA2. All the 5272-1G>A families shared a common haplotype in eight markers (1.1 Mb region) and the mutation age was estimated in 15 generations (approximately 380 years). A conserved haplotype associated to 5374delTATG was observed in four markers (0.82 Mb). The mutation occurred approximately 48 generations ago (approximately 1200 years). Each mutation likely arose from a common ancestor that could be traced to a small area of Castilla-León and expanded to other Spanish regions. They can have a significant impact on the clinical management of asymptomatic carriers as well as on the genetic screening strategy to be followed in populations with Spanish ancestries.

[Evaluation of lercanidipine in the general practice setting]. / Evaluación del lercanidipino en Atención Primaria: seguridad y eficacia. Resultados de estudio LAPSE.

OBJECTIVE: To determine the efficacy and tolerability of a long-acting dihydropyridine in the clinical settings of general practice. MATERIAL AND METHODS: 110 essential hypertensives were included (age 62.3 +/- 10.8 years, 51 men and 53 women, 38/ obese -IMC >30 kg/m2, ten diabetics). 104 patients ended the followup. Patients were treated with lercanidipine 10 mg once daily in the morning. Follow-up lasted 6 months. When blood pressure was not controlled (BP < 140/90 mmHg) in any visit, a second drug was added, excluding calcium channel blockers. Antiadrenergic drugs were recommended. If patients were not controlled ittwo consecutive visits they were excluded from follow-up. RESULTS: Significant reductions in both systolic (baseline 157.4 +/- 11.7 vs 131.1 +/- 6.8 mmHg, p < 0,001) and diastolic BP (baseline 94.7 +/- 5.8 vs 80.0 +/- 5.5 mmHg, p < 0,001) were attained at six months. Mean SBP decrease was 26.7 mmHg and mean DBP reduction was 15.6 mmHg. At the study end, 84.3/ of the patients achieved a BP < 140/90 mmHg. Thirty patients needed a second drug to become controlled (26 at the study end). The overall incidence of adverse effects was 4,4/ (n=6) and just three patients withdrew the treatment due to untoward effects. Plasmatic cholesterol lowered from 225.3 +/- 41.0 to 216.7 +/- 25.3 mg/dl (p = 0,03) and urate decreased from 5.6 +/- 1.6 to 5.1 +/- 1.4 mgldl, p = 0,03). CONCLUSIONS: Lercanidipine is a calcium channel blockers of high efficacy and low incidence of adverse effects in the clinical settings of general practice. It seems to have a positive metabolic effects on plasmatic levels of cholesterol and urate.