Dataset Information

Ethnicity-related DMD Genotype Landscapes in European and Non-European Countries.

ABSTRACT:

Objective

Genetic diagnosis and mutation identification are now compulsory for Duchenne (DMD) and Becker muscular dystrophies (BMD), which are due to dystrophin (DMD) gene mutations, either for disease prevention or personalized therapies. To evaluate the ethnic-related genetic assortments of DMD mutations, which may impact on DMD genetic diagnosis pipelines, we studied 328 patients with DMD and BMD from non-European countries.

Methods

We performed a full DMD mutation detection in 328 patients from 10 Eastern European countries (Poland, Hungary, Lithuania, Romania, Serbia, Croatia, Bosnia, Bulgaria, Ukraine, and Russia) and 2 non-European countries (Cyprus and Algeria). We used both conventional methods (multiplex ligation-dependent probe amplification [MLPA] followed by gene-specific sequencing) and whole-exome sequencing (WES) as a pivotal study ran in 28 patients where DMD mutations were already identified by standard techniques. WES output was also interrogated for DMD gene modifiers.

Results

We identified DMD gene mutations in 222 male patients. We identified a remarkable allele heterogeneity among different populations with a mutation landscape often country specific. We also showed that WES is effective for picking up all DMD deletions and small mutations and its adoption could allow a detection rate close to 90% of all occurring mutations. Gene modifiers haplotypes were identified with some ethnic-specific configurations.

Conclusions

Our data provide unreported mutation landscapes in different countries, suggesting that ethnicity may orient genetic diagnosis flowchart, which can be adjusted depending on the mutation type frequency, with impact in drug eligibility.

SUBMITTER: Selvatici R

PROVIDER: S-EPMC7768913 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Ethnicity-related DMD Genotype Landscapes in European and Non-European Countries.

Selvatici Rita R Rossi Rachele R Fortunato Fernanda F Trabanelli Cecilia C Sifi Yamina Y Margutti Alice A Neri Marcella M Gualandi Francesca F Szabò Lena L Fekete Balint B Angelova Lyudmilla L Litvinenko Ivan I Ivanov Ivan I Vildan Yurtsever Y Iuhas Oana Alexandra OA Vintan Mihaela M Burloiu Carmen C Lacramioara Butnariu B Visa Gabriela G Epure Diana D Rusu Cristina C Vasile Daniela D Sandu Magdalena M Vlodavets Dmitry D Mager Monica M Kyriakides Theodore T Delin Sanja S Lehman Ivan I Fureš Jadranka Sekelj JS Bojinova Veneta V Militaru Mariela M Guergueltcheva Velina V Burnyte Birute B Molnar Maria Judith MJ Butoianu Niculina N Bensemmane Selma Dounia SD Makri-Mokrane Samira S Herczegfalvi Agnes A Panzaru Monica M Emandi Adela Chirita AC Lusakowska Anna A Potulska-Chromik Anna A Kostera-Pruszczyk Anna A Shatillo Andriy A Khelladi Djawed Bouchenak DB Dendane Oussama O Fang Mingyan M Lu Zhiyuan Z Ferlini Alessandra A

Neurology. Genetics 20201224 1

<h4>Objective</h4>Genetic diagnosis and mutation identification are now compulsory for Duchenne (DMD) and Becker muscular dystrophies (BMD), which are due to dystrophin (<i>DMD</i>) gene mutations, either for disease prevention or personalized therapies. To evaluate the ethnic-related genetic assortments of <i>DMD</i> mutations, which may impact on DMD genetic diagnosis pipelines, we studied 328 patients with DMD and BMD from non-European countries.<h4>Methods</h4>We performed a full DMD mutatio ...[more]

PMID: 33376799

Similar Datasets

Project description:Objective: To review the reimbursement recommendations issued by selected European health technology assessment agencies for orphan drugs and the reimbursement status of these drugs; to assess the relationship between the type of recommendation and reimbursement status. Methods: The list of orphan drugs to be included in the analysis was obtained from the European Medicines Agency and Orphanet. Seven European states were included in the analysis: Belgium, England, France, Germany, Poland, Scotland, and Spain. For all identified orphan drugs, relevant data on the reimbursement status and type of recommendation were collected for each country. The relationship between the type of recommendation and reimbursement status was evaluated separately for each considered country, using Cohen's kappa coefficient for the measurement of agreement; sub-analyses for oncology and metabolic drugs were performed. Results: Most reimbursement recommendations for orphan drugs were positive (71%), while approximately 17% were negative and almost 13% were conditional. The highest percentage of positive reimbursement recommendations was observed in Spain (97%) and France (95%) and the highest percentage of negative reimbursement recommendations was revealed for Poland (49%). On average, 65% of the 163 analyzed orphan drugs were reimbursed from public funds. The highest number of reimbursed orphan drugs was observed in Germany (n = 148), while the lowest, in Poland (n = 41). Considering all analyzed drugs, the highest agreement between recommendations and reimbursement status was observed for Spain (value of 1), and the lowest, for Germany (? = -0.03). Conclusions: On average, more than 60% of identified orphan drugs were reimbursed from public funds in the included countries, and the majority of reimbursement recommendations were found to be positive. The agreement between reimbursement recommendations and reimbursement status differed between the countries, but overall, it did not show any patterns, as it ranged from -0.03 to 1 (? coefficient).

Project description:Currently, the world faces an existential threat of climate change, and every government across the globe is trying to come up with strategies to tackle the severity of climate change in every way possible. To this end, the use of clean energy rather than fossil fuel energy sources is critical, as it can reduce greenhouse gas emissions and pave the way for carbon neutrality. This study examines the impact of the energy cleanability gap on four different climate vulnerabilities, such as ecosystem, food, health, and housing vulnerabilities, considering 47 European and non-European high-income countries. The study considers samples from 2002 to 2019. This study precedes the empirical analysis in the context of a quadratic relationship between the energy cleanability gap and climate vulnerability. The study uses system-generalized methods of the moment as the main technique, while panel quantile regression is a robustness analysis. Fixed effect and random effect models have also been incorporated. The study finds that the energy cleanability gap and all four climate vulnerabilities demonstrate a U-shaped relationship in both European and non-European countries, implying that when the energy cleanability gap increases, climate vulnerability decreases, but after reaching a certain threshold, it starts to increase. Development expenditure is found to be negatively affecting food and health vulnerabilities in European nations, while it increases food vulnerability and decreases health vulnerability in non-European nations. Regarding industrialization's impact on climate vulnerabilities, the study finds opposite effects for the European and non-European economies. On the other hand, for both groups, trade openness decreases climate vulnerabilities. Based on these results, the study recommends speeding up the energy transition process from fossil fuel energy resources towards clean energy resources to obtain carbon neutrality in both European and non-European groups.

Project description:Mucormycosis has emerged as a rare but frequently fatal invasive fungal disease. Current knowledge on paediatric mucormycosis is based on case reports and small series reported over several decades. Contemporary data on a large cohort of patients is lacking.Two large international registries (Zygomyco.net and FungiScope™) were searched for mucormycosis cases in ?19 year-old patients. Cases enrolled between 2005 and 2014 were extracted, and dual entries in the two databases merged. Epidemiology, clinical characteristics, diagnostic procedures, therapeutic management and final outcome were recorded and analysed with SPSS v.12.Sixty-three unique cases (44 proven and 19 probable) were enrolled from 15 countries (54 in European and 9 in non-European countries). Median age was 13 years [Interquartile Range (IQR) 7.7] with a slight predominance (54.1 %) of females. Underlying conditions were haematological malignancies (46 %), other malignancies (6.3 %), haematopoietic stem cell transplantation (15.9 %), solid organ transplantation, trauma/surgery and diabetes mellitus (4.8 % each) and a variety of other diseases (7.9 %); in 9.5%, no underlying medical condition was found. Neutropenia was recorded in 46 % of the patients. The main sites of infection were lungs (19 %), skin and soft tissues (19 %), paranasal sinus/sino-orbital region (15.8 %) and rhino-cerebral region (7.9 %). Disseminated infection was present in 38.1 %. Mucormycosis diagnosis was based on several combinations of methods; culture combined with histology was performed in 31 cases (49.2 %). Fungal isolates included Rhizopus spp. (39.7 %), Lichtheimia spp. (17.5 %), Mucor spp. (12.7 %), Cunninghamella bertholletiae (6.3 %) and unspecified (23.8 %). Treatment comprised amphotericin B (AmB) monotherapy in 31.7 % or AmB in combination with other antifungals in 47.7 % of the cases, while 14.3 % received no antifungals. Surgery alone was performed in 6.3 %, and combined with antifungal therapy in 47.6 %. Crude mortality at last contact of follow-up was 33.3 %. In regression analysis, disseminated disease and prior haematopoietic stem cell transplantation were associated with increased odds of death, whereas the combination of systemic antifungal therapy with surgery was associated with improved survival.Paediatric mucormycosis mainly affects children with malignancies, presents as pulmonary, soft tissue, paranasal sinus or disseminated disease and is highly lethal. Outcome is improved when active antifungal therapy and surgery are combined.

Project description:The COMT (Catechol-O-Methyl Transferase) gene may influence a person's vulnerability to develop long-term pain and some COMT single nucleotide polymorphisms (SNPs) may associate with patterns of acute or chronic pain. Many patients with whiplash-associated disorders (WADs) suffer from long-term pain and other related symptoms, but it is less known if genetic factors play a role in the recovery process. The primary aim of this study was to evaluate whether self-reported non-recovery, including pain, was related to COMT genotype in patients with WAD. The secondary aim was to investigate whether or not background factors, including mental health, were related to genotype and non-recovery.A total of 133 patients with neck pain after a whiplash trauma were included. Background factors were collected and blood samples were taken during the acute phase after the accident. DNA was isolated from blood and used to genotype the SNPs rs6269, rs4633, rs4818 and rs4680 in the COMT gene; additionally haplotypes were estimated and haplogenotypes inferred. The patients were followed up after 12 months and asked to rate their recovery including pain, mental health and quality of life.The overall reported non-recovery rate at 12 months was 44% with no significant differences in distribution of the COMT haplotypes. High levels of self-reported pain (OR 7.2) and anxiety (OR 4.4) after the accident were associated with non-recovery, but not related to the haplotypes. None of the other background factors were related to the haplotypes or non-recovery.No association between self-reported non-recovery or pain levels and COMT haplotypes in patients with acute whiplash injuries could be detected. Independent replications are necessary to discard the hypothesis that COMT haplotypes do not influence non-recovery or pain levels in patients with acute whiplash injuries. High levels of initial pain and anxiety were associated with non-recovery, thereby confirming previously published reports.

Dataset Information

Ethnicity-related DMD Genotype Landscapes in European and Non-European Countries.

Objective

Methods

Results

Conclusions

Publications

Ethnicity-related DMD Genotype Landscapes in European and Non-European Countries.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets