Systematic Approach Revealed SERPING1 Splicing-Affecting Variants to be Highly Represented in the Czech National HAE Cohort.

Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) is a rare and life-threatening condition characterized by recurrent localized edema. We conducted a systematic screening of SERPING1 defects in a cohort of 207 Czech patients from 85 families with C1-INH-HAE. Our workflow involved a combined strategy of sequencing extended to UTR and deep intronic regions, advanced in silico prediction tools, and mRNA-based functional assays. This approach allowed us to detect a causal variant in all families except one and to identify a total of 56 different variants, including 5 novel variants that are likely to be causal. We further investigated the functional impact of two splicing variants, namely c.550 + 3A > C and c.686-7C > G using minigene assays and RT-PCR mRNA analysis. Notably, our cohort showed a considerably higher proportion of detected splicing variants compared to other central European populations and the LOVD database. Moreover, our findings revealed a significant association between HAE type 1 missense variants and a delayed HAE onset when compared to null variants. We also observed a significant correlation between the presence of the SERPING1 variant c.-21 T > C in the trans position to causal variants and the frequency of attacks per year, disease onset, as well as Clinical severity score. Overall, our study provides new insights into the genetic landscape of C1-INH-HAE in the Czech population, including the identification of novel variants and a better understanding of genotype-phenotype correlations. Our findings also highlight the importance of comprehensive screening strategies and functional analyses in improving the C1-INH-HAE diagnosis and management.

[Oncology secrets of suddenly deceased individuals]. / Onkologická tajemství zemrelých.

Malignant neoplasms represent the second most common cause of death in men and women in the Czech Republic after cardiovascular diseases. The incidence, prevalence and mortality is recorded in the Czech National Cancer Registry. The most recent data available is from 2013, in this year there were 81 541 patients newly diagnosed with cancer and 26 944 people died of cancer. From a long-term perspective, the incidence of neoplasms is increasing and the mortality is decreasing. In the Institute of Forensic Medicine in Brno there were 480 cases of newly reported malignant tumors during the period 2010-2015, which were not known before the autopsy. 71.4 % of these cases were men and 28.6 % were women. In 212 cases the tumor was advanced and was the immediate cause of death. The total number of deadly cases in men was 149, the age average was 66.2 years. The most common malignant tumor leading to death was of bronchi and lungs (39.6 %), large intestine (9.4 %), pancreas (6.7 %), liver (4.7 %), stomach (4 %) and prostatic gland (4 %). In women the total number of deaths resulting from malignant tumor was 63, the age average was 72.6 years. The most common malignant tumor leading to death was of bronchi and lungs (33.3%), ovary (11.1 %), large intestine (9.5 %), gall bladder (6.3 %) and kidney (6.3 %). Some of the autopsy findings are shown on the photographs at the end of the article.