Distinct Features of Probands With Early Repolarization and Brugada Syndromes Carrying SCN5A Pathogenic Variants

The purpose of the article is to research the history of creation and formation of the Chancellery of Contract Affairs – the first supervisory and regulatory body in the field of public procurement in Russia. The early history of the Contracting Chancellery (1715–1717) can be traced in the context of the development of legislative and administrative regulation of public procurement during the reign of Peter the Great. The institution of public procurement itself, according to the author, is associated with the acquisition of distinct features of the modern state by Russia, which was manifested in the previous time. The immediate impetus for the development of the institution was the reform of the armed forces and the resulting mobilization efforts of the supreme power. The very content of the research predetermined the use of source-based and historical-legal methods. As a result of the study, the author states that the creation of a special body – the Chancellery of Contract Affairs, designed to take control of the situation under state contracts, turned out to be the right decision. The well-coordinated work of the Contracting Chancellery with the Senate, fiscal authorities and investigative bodies led to the creation of a number of important regulatory legal acts, almost ‘from scratch’ forming the legislative basis for the institution of public procurement functioning. The need for further work on the designated topic is noted.

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Thiolatocobalamins repair the activity of pathogenic variants of the human cobalamin processing enzyme CblC

Biochimie ◽

10.1016/j.biochi.2020.10.006 ◽

2020 ◽

Author(s):

Victoria Wingert ◽

Srijan Mukherjee ◽

Anna J. Esser ◽

Sidney Behringer ◽

Segun Tanimowo ◽

...

Keyword(s):

Pathogenic Variants ◽

Processing Enzyme

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Contribution of SLC22A12 on hypouricemia and its clinical significance for screening purposes

Scientific Reports ◽

10.1038/s41598-019-50798-6 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 1

Author(s):

Do Hyeon Cha ◽

Heon Yung Gee ◽

Raul Cachau ◽

Jong Mun Choi ◽

Daeui Park ◽

...

Keyword(s):

Genetic Diagnosis ◽

Kidney Injury ◽

Genetic Identification ◽

Diagnostic Screening ◽

Renal Hypouricemia ◽

Pathogenic Variants ◽

Whole Exome ◽

Causal Variants ◽

Coding Variants ◽

Independent Cohort

Abstract Differentiating between inherited renal hypouricemia and transient hypouricemic status is challenging. Here, we aimed to describe the genetic background of hypouricemia patients using whole-exome sequencing (WES) and assess the feasibility for genetic diagnosis using two founder variants in primary screening. We selected all cases (N = 31) with extreme hypouricemia (<1.3 mg/dl) from a Korean urban cohort of 179,381 subjects without underlying conditions. WES and corresponding downstream analyses were performed for the discovery of rare causal variants for hypouricemia. Two known recessive variants within SLC22A12 (p.Trp258*, pArg90His) were identified in 24 out of 31 subjects (77.4%). In an independent cohort, we identified 50 individuals with hypouricemia and genotyped the p.Trp258* and p.Arg90His variants; 47 of the 50 (94%) hypouricemia cases were explained by only two mutations. Four novel coding variants in SLC22A12, p.Asn136Lys, p.Thr225Lys, p.Arg284Gln, and p.Glu429Lys, were additionally identified. In silico studies predict these as pathogenic variants. This is the first study to show the value of genetic diagnostic screening for hypouricemia in the clinical setting. Screening of just two ethnic-specific variants (p.Trp258* and p.Arg90His) identified 87.7% (71/81) of Korean patients with monogenic hypouricemia. Early genetic identification of constitutive hypouricemia may prevent acute kidney injury by avoidance of dehydration and excessive exercise.

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Lynch syndrome-related non-endometrioid endometrial cancer: analysis of outcomes

International Journal of Gynecological Cancer ◽

10.1136/ijgc-2019-000824 ◽

2019 ◽

Vol 30 (1) ◽

pp. 56-61

Author(s):

Giorgio Bogani ◽

Maria Grazia Tibiletti ◽

Maria Teresa Ricci ◽

Ileana Carnevali ◽

Viola Liberale ◽

...

Keyword(s):

Endometrial Cancer ◽

Lynch Syndrome ◽

Disease Free Survival ◽

Oncologic Outcomes ◽

Cox Models ◽

Matching Algorithm ◽

Pathogenic Variants ◽

Propensity Matching ◽

Endometrioid Endometrial Cancer

ObjectiveWomen with Lynch syndrome have a risk up to 40–60% of developing endometrial cancer, which is higher than their risk of developing colorectal or ovarian cancer. To date, no data on the outcomes of patients with Lynch syndrome diagnosed with non-endometrioid endometrial cancer are available. The goal of this study was to evaluate the outcome of patients with Lynch syndrome diagnosed with non-endometrioid endometrial cancer.MethodsData from consecutive patients diagnosed with Lynch syndrome and with a histological diagnosis of non-endometrioid endometrial cancer were retrospectively collected in two referral institutes in Italy. A case–control comparison (applying a propensity matching algorithm) was performed in order to compare patients with proven Lynch syndrome and controls. Inclusion criteria were: (a) histologically-proven endometrial cancer; (b) detection of a germline pathogenic variant in one of the MMR genes; (c) adequate follow-up. Only carriers of pathogenic or likely pathogenic variants (ie, class 5 and 4 according to the InSiGHT classification) were included in the study. Survival outcomes were assessed using KaplanMeier and Cox models.ResultsOverall, 137 patients with Lynch syndrome were collected. Mean patient age was 49.2 (10.9) years. Genes involved in the Lynch syndrome included MLH1, MSH2, and MSH6 in 43%, 39%, and 18% of cases, respectively. The study population included 27 patients with non-endometrioid endometrial cancer, who were matched 1:2 with patients with sporadic cancers using a propensity matching algorithm. After a median follow-up of 134 months (range 1–295), 2 (7.4%) of the 27 patients developed recurrent disease (3 and 36 months) and subsequently died of disease (7 and 91 months). Patients diagnosed with Lynch syndrome experienced better disease-free survival (HR 7.86 (95% CI 1.79 to 34.5); p=0.006) and overall survival (HR 5.33 (95% CI 1.18 to 23.9); p=0.029) than controls.ConclusionsNon-endometrioid endometrial cancer occurring in patients with Lynch syndrome might be associated with improved oncologic outcomes compared with controls. Genetic/molecular profiling should be investigated in order to better understand the mechanism underlying the prognosis.

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