Sociocultural, spiritual, moral and tutor support for people with disabilities in the conditions of institutions of higher education (project)

Актуальність дослідження розглядається у площині еволюції у сфері освіти та особистості з інвалідністю в умовах нової моделі інклюзивного простору. Україна, ратифікувавши Лісабонську конвенцію та приєднавшись до Болонської декларації, також повинна виконувати всі взяті на себе зобов’язання. Це передусім стосується стратегічного пріоритету забезпечення рівності та соціальної взаємодії в рамках Європейської співпраці в освіті. Власне Україна, як учасниця Болонського процесу, повинна використовувати роль освіт як ключовий інструмент досягнення успішного соціального захисту та розвитку моделі соціальної інклюзії осіб із особливими потребами/інвалідністю. Соціально-культурний, тьюторський та духовно-моральний супровід на основі отриманого досвіду, має надати студентам закладів вищої освіти допомогу на шляху самостійного вибору соціально-культурної та особистісної позиції, можливість впевнено висловлювати свою думку, бути активним, мати власну громадську позицію, враховуючи моральні принципи та духовну внутрішню наповненість. Стаття має на меті продемонструвати проєкт та описати його технологію в процесі реалізації проєктної діяльності, розробленої з урахуванням відсутності узгодження соціальних механізмів та умов культурної активності особистості з обмеженими можливостями та орієнтований на розвиток творчих, культурно-дозвіллєвих та соціальних потреб студентів з інвалідністю в умовах закладів вищої освіти. Соціально-культурний та духовно-моральний супровід розглядається як створення у закладах вищої освіти умов для ефективної, спрямованої та активної самореалізації студентів у навчально-виховному процесі, а, надалі, використання отриманих навичок та позитивного досвіду в соціальній, особистісній та міжособистісній сфері, трудовій та культурній діяльності з урахуванням їхніх психофізичних можливостей, інтересів, принципів та уподобань. Підкреслюється важливість включення тьютора в освітній процес студента, який має мобілізувати внутрішні резерви вихованця для того, щоб у подальшому той сам міг впоратися зі своїми труднощами

Whole-exome sequencing identifies de novo mutation in the COL1A1 gene to underlie the severe osteogenesis imperfecta

Background Osteogenesis imperfecta (OI) comprises a clinically and genetically heterogeneous group of connective tissue disorders, characterized by low bone mass, increased bone fragility, and blue-gray eye sclera. OI often results from missense mutations in one of the conserved glycine residues present in the Gly-X-Y sequence repeats of the triple helical region of the collagen type I α chain, which is encoded by the COL1A1 gene. The aim of the present study is to describe the phenotype of OI II patient and a novel mutation, causing current phenotype. Results We report an undescribed de novo COL1A1 mutation in a patient affected by severe OI. After performing the whole-exome sequencing in a case parent–child trio, we identified a novel heterozygous c.2317G > T missense mutation in the COL1A1 gene, which leads to p.Gly773Cys transversion in the triple helical domain of the collagen type I α chain. The presence of the missense mutation was confirmed with the Sanger sequencing. Conclusions Hereby, we report a novel mutation in the COL1A1 gene causing severe, life threatening OI and indicate the role of de novo mutation in the pathogenesis of rare familial diseases. Our study underlines the importance of exome sequencing in disease gene discovery for families where conventional genetic testing does not give conclusive evidence

Phenotypic variation in Vietnamese osteogenesis imperfecta patients sharing a recessive P3H1 pathogenic variant

Osteogenesis imperfecta (OI) is a syndromic disorder of bone fragility with high variation in its clinical presentation. Equally variable is molecular aetiology; recessive forms are caused by approximately 20 different genes, many of which are directly implicated in collagen type I biosynthesis. Biallelic variants in prolyl 3-hydroxylase 1 (P3H1) are known to cause severe OI by affecting the competence of the prolyl 3-hydroxylation—cartilage associated protein—peptidyl-prolyl cis-trans isomerase B (P3H1-CRTAP-CyPB) complex, which acts on the Pro986 residue of collagen type I α 1 (COL1A1) and Pro707 collagen type I α 2 (COL1A2) chains. The investigation of an OI cohort of 146 patients in Vietnam identified 14 families with P3H1 variants. The c.1170+5G>C variant was found to be very prevalent (12/14) and accounted for 10.3% of the Vietnamese OI cohort. New P3H1 variants were also identified in this population. Interestingly, the c.1170+5G>C variants were found in families with the severe clinical Sillence types 2 and 3 but also the milder types 1 and 4. This is the first time that OI type 1 is reported in patients with P3H1 variants expanding the clinical spectrum. Patients with a homozygous c.1170+5G>C variant shared severe progressively deforming OI type 3: bowed long bones, deformities of ribcage, long phalanges and hands, bluish sclera, brachycephaly, and early intrauterine fractures. Although it remains unclear if the c.1170+5G>C variant constitutes a founder mutation in the Vietnamese population, its prevalence makes it valuable for the molecular diagnosis of OI in patients of the Kinh ethnicity. Our study provides insight into the clinical and genetic variation of P3H1-related OI in the Vietnamese population

Featured Article: Transcriptional landscape analysis identifies differently expressed genes involved in follicle-stimulating hormone induced postmenopausal osteoporosis

Osteoporosis is a disorder associated with bone tissue reorganization, bone mass, and mineral density. Osteoporosis can severely affect postmenopausal women, causing bone fragility and osteoporotic fractures. The aim of the current study was to compare blood mRNA profiles of postmenopausal women with and without osteoporosis, with the aim of finding different gene expressions and thus targets for future osteoporosis biomarker studies. Our study consisted of transcriptome analysis of whole blood serum from 12 elderly female osteoporotic patients and 12 non-osteoporotic elderly female controls. The transcriptome analysis was performed with RNA sequencing technology. For data analysis, the edgeR package of R Bioconductor was used. Two hundred and fourteen genes were expressed differently in osteoporotic compared with non-osteoporotic patients. Statistical analysis revealed 20 differently expressed genes with a false discovery rate of less than 1.47 × 10−4 among osteoporotic patients. The expression of 10 genes were up-regulated and 10 down-regulated. Further statistical analysis identified a potential osteoporosis mRNA biomarker pattern consisting of six genes: CACNA1G, ALG13, SBK1, GGT7, MBNL3, and RIOK3. Functional ingenuity pathway analysis identified the strongest candidate genes with regard to potential involvement in a follicle-stimulating hormone activated network of increased osteoclast activity and hypogonadal bone loss. The differentially expressed genes identified in this study may contribute to future research of postmenopausal osteoporosis blood biomarkers

Potential osteoporosis MRNA biomarkers discovered in transcriptome study of Estonian postmenopausal female patients

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Correlation of the first fracture time and COL1A1/2 mutations in patients with Osteogenesis Imperfecta

Osteogenesis Imperfecta (OI) is a brittle bone disease, characterized with reduced bone mass and bone fragility of different severity due to collagen type I defects. Patients suffer from recurrent spontaneous fractures starting in the early childhood or before birth. The main aim of the study was to relate time of the first fracture with COL1A1/2 mutations causing OI. Total number of 167 unrelated OI patients from the Osteogenesis Imperfecta database of Tartu University Department of Traumatology and Orthopeadics, were included in the study. Data of OI genotypes was recruited from previous Sanger sequencing mutational analysis of the COL1A1/2 genes. Time of the first fracture was recorded from patients’ words and divided into categories: intrauterine, perinatal, 0–6 and ≥7 years old. Significance of correlations between time of the first fracture and COL1A1/2 mutations was tested with Fisher’s test. Among 167 analysed patients, 29 (17.37%) had intrauterine fractures, 21 (12.57%) had perinatal fractures, 106 (63.47%) had fractures at the age 0–6 years old, 8 patients (4.79%) at ≥7 years old, and 3 (1.80%) patients had no fractures. Number of patients harbouring collagen I mutations was 103 (61.68%). The statistically significant correlation between the first fracture time and COL1A1/2 mutations was highlighted during the study (P=0.0288). Exploring of the relation between type of the COL1A1/2 mutations and time of the first fracture, showed connection between quality collagen mutations and earlier time of the first fracture (P=0.0414). Intrauterine fractures did not reveal correlation with presence of the COL1A1/2 mutations (P=0.8339), however showed correlation with collagen I quality mutations (P=0.0270). Perinatal fractures, represented mostly with fractures happened during delivery, did not reveal correlations with presence (P=0.8180) or type (P=1) of the COL1A1/2 mutations. Our results show general correlation between time of the first fracture and presence of the COL1A1/2 mutations. Quality collagen mutations are related to the earlier time of the first fracture. Despite the clear genetic background of bone fragility phenotype in OI patients, minor variations in time of the first fracture in OI patients might come from additional non-genetic factors

From Genetics to Clinical Implications: A Study of 675 Dutch Osteogenesis Imperfecta Patients

Osteogenesis imperfecta (OI) is a heritable connective tissue disorder that causes bone fragility due to pathogenic variants in genes responsible for the synthesis of type I collagen. Efforts to classify the high clinical variability in OI led to the Sillence classification. However, this classification only partially takes into account extraskeletal manifestations and the high genetic variability. Little is known about the relation between genetic variants and phenotype as of yet. The aim of the study was to create a clinically relevant genetic stratification of a cohort of 675 Dutch OI patients based on their pathogenic variant types and to provide an overview of their respective medical care demands. The clinical records of 675 OI patients were extracted from the Amsterdam UMC Genome Database and matched with the records from Statistics Netherlands (CBS). The patients were categorized based on their harbored pathogenic variant. The information on hospital admissions, outpatient clinic visits, medication, and diagnosis-treatment combinations (DTCs) was compared between the variant groups. OI patients in the Netherlands appear to have a higher number of DTCs, outpatient clinic visits, and hospital admissions when compared to the general Dutch population. Furthermore, medication usage seems higher in the OI cohort in comparison to the general population. The patients with a COL1A1 or COL1A2 dominant negative missense non-glycine substitution appear to have a lower health care need compared to the other groups, and even lower than patients with COL1A1 or COL1A2 haploinsufficiency. It would be useful to include the variant type in addition to the Sillence classification when categorizing a patient’s phenotype

Medical Care Use Among Patients with Monogenic Osteoporosis Due to Rare Variants in LRP5, PLS3, or WNT1

Pathogenic variants in the LRP5, PLS3, or WNT1 genes can significantly affect bone mineral density, causing monogenic osteoporosis. Much remains to be discovered about the phenotype and medical care needs of these patients. The purpose of this study was to examine the use of medical care among Dutch individuals identified between 2014 and 2021 with a pathogenic or suspicious rare variant in LRP5, PLS3, or WNT1. In addition, the aim was to compare their medical care utilization to both the overall Dutch population and the Dutch Osteogenesis Imperfecta (OI) population. The Amsterdam UMC Genome Database was used to match 92 patients with the Statistics Netherlands (CBS) cohort. Patients were categorized based on their harbored variants: LRP5, PLS3, or WNT1. Hospital admissions, outpatient visits, medication data, and diagnosis treatment combinations (DTCs) were compared between the variant groups and, when possible, to the total population and OI population. Compared to the total population, patients with an LRP5, PLS3, or WNT1 variant had 1.63 times more hospital admissions, 2.0 times more opened DTCs, and a greater proportion using medication. Compared to OI patients, they had 0.62 times fewer admissions. Dutch patients with an LRP5, PLS3, or WNT1 variant appear to require on average more medical care than the total population. As expected, they made higher use of care at the surgical and orthopedic departments. Additionally, they used more care at the audiological centers and the otorhinolaryngology (ENT) department, suggesting a higher risk of hearing-related problems

A standard set of outcome measures for the comprehensive assessment of osteogenesis imperfecta

Background: Osteogenesis Imperfecta (OI) is a genetic disorder also known as ‘brittle bone disease’. The clinical manifestation of OI shows a wide variation. Therefore, care for patients with OI requires an interdisciplinary approach. The effectiveness of particular interventions and treatment protocols of interdisciplinary teams is not clear due to a non-standardized and wide variation of patient outcomes thus making the comparison of outcome measures available in the literature difficult. It is only by agreeing on a common, standard set of outcome measures for the comprehensive appraisal of OI that comparisons across interdisciplinary treatment centers for OI will be possible in the future. Methods: The Key4OI international interdisciplinary working group of 27 members used a consensus-driven modified Delphi approach to develop a set of global outcome measures for patients with OI. The International Classification of Functioning, Disability and Health (ICF), was used to define domains and organize the outcomes from the literature search. After reviewing the outcomes extracted from the literature, trials and registries, the working group agreed on a final selection of domains and their definition (ICF definition as well as a lay description). These domains were then presented to the focus groups who prioritized the outcome domains by taking into account the items important to the OI community. All content was collected and analyzed and final domains were determined. A consensus of appropriate measuring instruments for each domain was reached with Delphi rounds. The entire approach was in line with the International Consortium for Health Outcomes Measurement ICHOM methodology. Results: More than 400 different outcome measures were identified in our literature search. After three Delphi rounds, 24 domains were selected. After the focus group sessions, the number of domains were reduced to 15. A consensus was reached on the measuring instruments to cover these domains for both children and adults. Conclusion: The Key4OI project resulted in standard set of outcome measures focused on the needs and wishes of individuals with OI and their families. This outcome set will enable healthcare teams and systems to compare and to improve their care pathways and quality of care worldwide. Further studies are needed to evaluate the implementation of this standardized outcome set