The optimal modeling method of specific tuberculosis peritonitis (experimental research)

The objective: to create a reproducible model of chronic tuberculosis peritonitis to study pathophysiological mechanisms of its progression and to develop pathogenetically based therapy.Subjects and Methods. The study was performed using 10 male rabbits of the Chinchilla breed. The animals were administered intraperitoneal culture of Mycobacterium tuberculosis, tuberculosis peritonitis modeling was performed according to the proposed method.Results. In the course of the experiment, it was proved that all animals developed tuberculous peritonitis with lesions of the large omentum and serous integuments of internal organs. Molecular genetic tests of fragments of the omentum and peritoneum detected DNA of Mycobacterium tuberculosis.

Non-invasive prenatal diagnosis of a paternally inherited MEN1 pathogenic splicing variant

Context Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disease caused by mutations in the tumor suppressor gene MEN1. The uncertainty of pathogenicity of MEN1 variants complexifies the selection of the patients likely to benefit from specific care. Objective MEN1-mutated patients should be offered tailored tumor screening and genetic counselling. We present a patient with hyperparathyroidism for whom genetic analysis identified a variant of uncertain significance in the MEN1 gene (NM_130799.2): c.654G>T p.(Arg218=). Additional functional genetic tests were performed to classify the variant as pathogenic and allowed prenatal testing. Design Targeted next generation sequencing identified a synonymous variant in the MEN1 gene in a 26-year-old male with symptomatic primary hyperparathyroidism. In silico and in vitro genetic tests were performed to assess variant pathogenicity. Results Genetic testing of the proband’s unaffected parents showed the variant occurred de novo. Transcript study showed a splicing defect leading to an in-frame deletion. The classification of the MEN1 variant as pathogenic confirmed the diagnosis of MEN1 and recommended an adapted medical care and follow-up. Pathogenic classification also allowed to propose a genetic counselling to the proband and his wife. Non-invasive prenatal diagnosis was performed with a personalized medicine-based protocol by detection of the paternally inherited variant in maternal plasmatic cell free DNA, using digital PCR. Conclusion We showed that functional genetic analysis can help to assess the pathogenicity of a MEN1 variant with crucial consequences for medical care and genetic counselling decisions.

Teniases caused by Taenia asiatica, Taenia saginata, Taenia solium

The urgency of the problem of human teniases is due to the widespread prevalence of these parasitoses, which often infect humans.The aim and result of the work is to summarize the available information about the etiology, epidemiology, pathogenesis, clinical picture, diagnosis, etiotropic therapy and prevention of human teniases.Conclusion. Teniases are widespread, including on the territory of Russia. The clinic mainly includes symptoms of lesions of the gastrointestinal tract, allergic reactions. Diagnostics is carried out on the basis of the detection of eggs, proglottids, coproangigens of parasites in the feces, serological and molecular genetic tests. Praziquantel is an effective etiotropic therapy. Prevention takes into account the peculiarities of the epidemiology of teniases.

Genes of Congenital Dermatologic Disorders in Dogs—A Review

This article presents an overview of up-to-date identified genes responsible for congenital canine skin diseases of dogs and the characteristics of these diseases. Congenital skin diseases constitute a specific group of dermatologic disorders that plays an important role in breeding of purebred dogs. They include primary seborrhoea, ichthyosis, hereditary nasal parakeratosis, dermatomyositis, colour dilution alopecia, skin mucinosis, dermoid sinus, lethal acrodermatitis, acral mutilation syndrome, keratoconjunctivitis sicca, ichthyosiform dermatosis, bullous epidermolysis, exfoliative dermal lupus erythematosus, congenital footpad hyperkeratosis and sebaceous adenitis. In the majority of cases, their occurrence is linked to particular breeds. In more than half of these diseases a specific defective gene variant responsible for the disease has been identified. Genetic tests for identification of the relevant defective genes serve as an important tool in the diagnostics of diseases in veterinary practice and in breeding of purebred dogs.

Genetic testing is necessary for correct diagnosis and treatment in patients with isolated methylmalonic aciduria: a case report

Background Isolated methylmalonic aciduria can be caused by pathogenic mutations in the gene for methylmalonyl-CoA mutase or in the genes encoding enzymes involved in the intracellular metabolism of cobalamin. Some of these mutations may be cobalamin responsive. The type of methylmalonic aciduria cannot always be assumed from clinical manifestation and the responsiveness to cobalamin has to be assessed for appropriate cobalamin administration, or to avoid unnecessary treatment. The cases presented herein highlight the importance of genetic testing in methylmalonic aciduria cases and the need for standardisation of the in vivo cobalamin-responsiveness assessment. Case presentation We describe two patients who presented in the first week of life with rapid neurological deterioration caused by metabolic acidosis with severe hyperammonaemia requiring extracorporeal elimination in addition to protein restriction, energy support, carnitine, and vitamin B12 treatment. The severity of the clinical symptoms and high methylmalonic acid concentrations in the urine (>30,000 μmol/mmol of creatinine) without hyperhomocysteinaemia in both of our patients suggested isolated methylmalonic aciduria. Based on the neonatal manifestation and the high methylmalonic acid urine levels, we assumed the cobalamin non-responsive form. The in vivo test of responsiveness to cobalamin was performed in both patients. Patient 1 was evaluated as non-responsive; thus, intensive treatment with vitamin B12 was not used. Patient 2 was responsive to cobalamin, but the dose was decreased to 1 mg i.m. every two weeks with daily oral treatment due to non-compliance. Genetic tests revealed bi-allelic mutations in the genes MMAB and MMAA in Patient 1 and 2, respectively. Based on these results, we were able to start intensive treatment with hydroxocobalamin in both patients. After the treatment intensification, there was no acute crisis requiring hospitalisation in Patient 1, and the urine methylmalonic acid levels further decreased in Patient 2. Conclusions Despite carrying out the in vivo test of responsiveness to cobalamin in both patients, only the results of molecular genetic tests led us to the correct diagnosis and enabled intensive treatment with hydroxocobalamin. The combination of the standardized in vivo test of cobalamin responsiveness and genetic testing is needed for accurate diagnosis and appropriate treatment of isolated methylmalonic aciduria.

IZAZOVI PRAVNOG UREĐENJA UPOTREBE OSOBNIH PODATAKA IZ GENSKIH TESTOVA U SVRHU OSIGURANJA

The paper deals with the issue of using genetic tests for insurance purposes. After introductory remarks, the paper provides an overview of various international and European legal sources both on data protection in general, and on the protection of data from genetic tests. The paper then researches into different solutions proposed by comparative law concerning the use of data from genetic tests for insurance purposes. Some solutions explicitly ban the use of genetic tests for insurance purposes (France, Austria, Portugal, Croatia), while others adopt a more liberal approach, allowing for its use (the USA, the UK, Germany). It is concluded that personal data protection does not exclude the possibility using data from genetic tests for insurance purposes, which proves the need for a common EU approach to the issue.

Direct-to-consumer genetic testing: Prospective users’ attitudes toward information about ancestry and biological relationships

Direct-to-consumer genetic testing is marketed as a tool to uncover ancestry and kin. Recent studies of actual and potential users have demonstrated that individuals’ responses to the use of these tests for these purposes are complex, with privacy, disruptive consequences, potential for misuse, and secondary use by law enforcement cited as potential concerns. We conducted six focus groups with a diverse sample of participants (n = 62) who were aware of but had not used direct-to-consumer genetic tests, in an effort to understand more about what people considering these tests think about the potential value, risks, and benefits of such testing, taking into account use by third parties, such as potential kin and law enforcement. Participants differed widely in the perceived value of direct-to-consumer genetic tests for ancestry and kinship information for their own lives, including the desirability of contact with previously unknown relatives. Some perceived ancestry testing as mere curiosity or entertainment, while others, particularly those who had gaps in their family history, few living relatives, or who were adopted, saw greater value. Concerns about intrusion into one’s life by purported kin and control of data were widespread, with many participants expressing concern about secondary uses of data that could harm users or their families. The use of direct-to-consumer genetic tests data for forensic genealogy elicited a particularly wide array of reactions, both spontaneously and in response to specific discussion prompts, mirroring the current public debate about law enforcement access to such data. The themes uncovered through our investigation warrant specific attention in the continued development of the science, policy, and practice of commercial direct-to-consumer genetic testing.

Genetic testing in endocrinology

This chapter begins with describing the genetic basis of endocrine disease, and the potential utility for genetic testing (alongside consent). It then covers different types of genetic tests and their applications. There is a section on pituitary adenomas, MEN types 1 and 4, familial isolated pituitary adenoma, and various other genetic conditions related to the endocrine system.