Genotype-phenotype correlations in FSHD

Abstract Background Facial-scapular-humeral myodystrophy Landouzy-Dejerine (FSHD) is an autosomal dominant disease, the basis of its pathogenesis is ectopic expression of the transcription factor DUX4 in skeletal muscle. There are two types of the disease: FSHD1 (MIM:158900) and FSHD2 (MIM: 158901), which have different genetic causes but are phenotypically indistinguishable. In FSHD1, partial deletion of the D4Z4 repeats on the 4th chromosome affects the expression of DUX4, whereas FSHD2 is caused by the mutations in the protein regulating the methylation status of chromatin - SMCHD1. High variability of clinical picture, both intra - and inter-family indicates a large number of factors influencing clinical picture. There are key genetic, epigenetic and gender factors that influence the expressivity and penetrance of the disease. Using only one of these factors allows just a rough prediction of the course of the disease, which indicates the combined effect of all of the factors on the DUX4 expression and on the clinical picture. Results In this paper, we analyzed the impact of genetic, epigenetic and gender differences on phenotype and the possibility of using them for disease prognosis and family counselling. Conclusions Key pathogenesis factors have been identified for FSHD. However, the pronounced intra - and inter-family polymorphism of manifestations indicates a large number of modifiers of the pathological process, many of which remain unknown

FSHD1 Diagnosis in a Russian Population Using a qPCR-Based Approach

Facioscapulohumeral dystrophy (FSHD) is an autosomal dominant myodystrophy. Approximately 95% of cases of FSHD are caused by partial deletion of the D4Z4 macrosatellite tandem repeats on chromosome 4q35. The existing FSHD1 diagnostic methods are laborious and not widely used. Here, we present a comprehensive analysis of the currently used diagnostic methods (Southern blotting and molecular combing) against a new qPCR-based approach for FSHD1 diagnosis. We observed 93% concordance between the results obtained by the new qPCR-based approach, reference Southern blotting and molecular combing methods. Applying the qPCR-based approach in the studied population, we observed a prevalence (64.9%) of the permissive alleles in the range of 3–6 D4Z4 units for a group of patients, while in a group of carriers, the permissive alleles were mostly (84.6%) present in the range of 6–9 D4Z4 units. No prevalence of disease penetrance depending on gender was observed. The results confirmed the earlier established inverse correlation between permissive allele size and disease severity, disease penetrance. The results suggest the applicability of the qPCR-based approach for FSHD1 diagnosis and its robustness in a basic molecular genetics laboratory. To our knowledge, this is the first study of FSHD1 permissive allele distribution in a Russian population

Diagnostic value of measured hemodynamic parameters: cardiac output, minute volume and a complete set of phase-related volumes of blood

The paper reviews the existing methods for hemodynamic parameters measurement, namely the Fick method, the thermodilution technique and the Cardiocode technology. Comparative analysis of the above methods is presented. Strong and weak points in each method and their informative values are identified. Distinctive features of the Cardiocode method, as the only noninvasive one, are described

Additional file 1: Table S1. of Mutations in gonadotropin-releasing hormone signaling pathway in two nIHH patients with successful pregnancy outcomes

Primers for bidirectional Sanger sequencing in nIHH patients. (DOCX 15 kb

The Results of Laboratory Studies of the Device for Evaluation of Suitability of Potato Tubers for Mechanized Harvesting

The purpose of this study is to substantiate the concept of a device for the evaluation of the suitability of varieties and hybrids of potato tubers for mechanical harvesting from the earliest stages of the selection process and to perform quantitative and structural assessment of damage to potato varieties and hybrids inflicted by the device, simulating the process of the harvester’s separating element operation depending on the machine type and harvesting conditions. The structural and operating diagram of the device for the evaluation of suitability of varieties and hybrids for mechanized harvesting has been developed, and the procedure and results of the study to determine the force action of the separating surface of the developed device on the potato tubers are presented. The device developed in accordance with the proposed conceptual scheme, further calibrated to account for modern potato harvesters would make it possible to conduct targeted selection of varieties suitable for mechanized cultivation, as well as to assess the degree of resistance of potato varieties to mechanized harvesting at early stages of selective and seed production works

The Results of Laboratory Studies of the Device for Evaluation of Suitability of Potato Tubers for Mechanized Harvesting

The purpose of this study is to substantiate the concept of a device for the evaluation of the suitability of varieties and hybrids of potato tubers for mechanical harvesting from the earliest stages of the selection process and to perform quantitative and structural assessment of damage to potato varieties and hybrids inflicted by the device, simulating the process of the harvester’s separating element operation depending on the machine type and harvesting conditions. The structural and operating diagram of the device for the evaluation of suitability of varieties and hybrids for mechanized harvesting has been developed, and the procedure and results of the study to determine the force action of the separating surface of the developed device on the potato tubers are presented. The device developed in accordance with the proposed conceptual scheme, further calibrated to account for modern potato harvesters would make it possible to conduct targeted selection of varieties suitable for mechanized cultivation, as well as to assess the degree of resistance of potato varieties to mechanized harvesting at early stages of selective and seed production works