High proportion of recurrent germline mutations in the BRCA1 gene in breast and ovarian cancer patients from the Prague area

BACKGROUND: Germline mutations in the BRCA1 and BRCA2 genes have been shown to account for the majority of hereditary breast and ovarian cancers. The purpose of our study was to estimate the incidence and spectrum of pathogenic mutations in BRCA1/2 genes in high-risk Czech families. METHODS: A total of 96 Czech families with recurrent breast and/or ovarian cancer and 55 patients considered to be at high-risk but with no reported family history of cancer were screened for mutations in the BRCA1/2 genes. The entire coding sequence of each gene was analyzed using a combination of the protein truncation test and direct DNA sequencing. RESULTS: A total of 35 mutations in the BRCA1/2 genes were identified in high-risk families (36.5%). Pathogenic mutations were found in 23.3% of breast cancer families and in 59.4% of families with the occurrence of both breast and ovarian cancer. In addition, four mutations were detected in 31 (12.9%) women with early onset breast cancer. One mutation was detected in seven (14.3%) patients affected with both a primary breast and ovarian cancer and another in three (33.3%) patients with a bilateral breast cancer. A total of 3 mutations in BRCA1 were identified among 14 (21.4%) women with a medullary breast carcinoma. Of 151 analyzed individuals, 35 (23.2%) carried a BRCA1 mutation and 9 (6.0%) a BRCA2 mutation. One novel truncating mutation was found in BRCA1 (c.1747A>T) and two in BRCA2 (c.3939delC and c.5763dupT). The 35 identified BRCA1 mutations comprised 13 different alterations. Three recurrent mutations accounted for 71.4% of unrelated individuals with detected gene alterations. The BRCA1 c.5266dupC (5382insC) was detected in 51.4% of mutation positive women. The mutations c.3700_3704del5 and c.181T>G (300T>G) contributed to 11.4% and 8.6% of pathogenic mutations, respectively. A total of eight different mutations were identified in BRCA2. The novel c.5763dupT mutation, which appeared in two unrelated families, was the only recurrent alteration of the BRCA2 gene identified in this study. CONCLUSION: Mutational analysis of BRCA1/2 genes in 151 high-risk patients characterized the spectrum of gene alterations and demonstrated the dominant role of the BRCA1 c.5266dupC allele in hereditary breast and ovarian cancer

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Advanced molecular approaches pave the road to a clear-cut diagnosis of hereditary retinal dystrophies.

Purpose: The aim of this study was to identify the molecular genetic basis of hereditary retinal dystrophies (HRDs) in five unrelated Iranian families. Methods: Whole exome sequencing and Sanger sequencing were performed in all families. Variants were analyzed using various bioinformatics databases and software. Results: Based on the selected strategies, we identified potentially causative variants in five families with HRDs: the novel homozygous deletion mutation c.586_589delTTTG (p.F196Sfs*56) in the TTC8 gene of family A, the novel homozygous missense mutation c.2389T>C (p.S797P) in the CRB1 gene in family B, the novel homozygous frameshift mutation c.2707dupA (p.S903Kfs*66) in the LRP5 gene in family C, the novel homozygous splice mutation c.584–1G>T in the MERTK gene in family D, and the novel homozygous missense mutation c.1819G>C (p.G607R) rs61749412 in the ABCA4 gene of family E. Conclusions: This study highlights the presence of five novel variants associated with retinal dystrophies in selected Iranian families with hereditary blindness

Kuluttajabarometri maakunnittain 2000, 2. neljännes

Suomen virallinen tilasto (SVT