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  1. Article ; Online: RINT1 deficiency disrupts lipid metabolism and underlies a complex hereditary spastic paraplegia

    Nathalie Launay / Montserrat Ruiz / Laura Planas-Serra / Edgard Verdura / Agustí Rodríguez-Palmero / Agatha Schlüter / Leire Goicoechea / Cristina Guilera / Josefina Casas / Felix Campelo / Emmanuelle Jouanguy / Jean-Laurent Casanova / Odile Boespflug-Tanguy / Maria Vazquez Cancela / Luis González Gutiérrez-Solana / Carlos Casasnovas / Estela Area-Gomez / Aurora Pujol

    The Journal of Clinical Investigation, Vol 133, Iss

    2023  Volume 14

    Abstract: The Rad50 interacting protein 1 (Rint1) is a key player in vesicular trafficking between the ER and Golgi apparatus. Biallelic variants in RINT1 cause infantile-onset episodic acute liver failure (ALF). Here, we describe 3 individuals from 2 unrelated ... ...

    Abstract The Rad50 interacting protein 1 (Rint1) is a key player in vesicular trafficking between the ER and Golgi apparatus. Biallelic variants in RINT1 cause infantile-onset episodic acute liver failure (ALF). Here, we describe 3 individuals from 2 unrelated families with novel biallelic RINT1 loss-of-function variants who presented with early onset spastic paraplegia, ataxia, optic nerve hypoplasia, and dysmorphic features, broadening the previously described phenotype. Our functional and lipidomic analyses provided evidence that pathogenic RINT1 variants induce defective lipid–droplet biogenesis and profound lipid abnormalities in fibroblasts and plasma that impact both neutral lipid and phospholipid metabolism, including decreased triglycerides and diglycerides, phosphatidylcholine/phosphatidylserine ratios, and inhibited Lands cycle. Further, RINT1 mutations induced intracellular ROS production and reduced ATP synthesis, affecting mitochondria with membrane depolarization, aberrant cristae ultrastructure, and increased fission. Altogether, our results highlighted the pivotal role of RINT1 in lipid metabolism and mitochondria function, with a profound effect in central nervous system development.
    Keywords Metabolism ; Neuroscience ; Medicine ; R
    Subject code 572 ; 570
    Language English
    Publishing date 2023-07-01T00:00:00Z
    Publisher American Society for Clinical Investigation
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Epigenetic profiling linked to multisystem inflammatory syndrome in children (MIS-C)

    Veronica Davalos / Carlos A. García-Prieto / Gerardo Ferrer / Sergio Aguilera-Albesa / Juan Valencia-Ramos / Agustí Rodríguez-Palmero / Montserrat Ruiz / Laura Planas-Serra / Iolanda Jordan / Iosune Alegría / Patricia Flores-Pérez / Verónica Cantarín / Victoria Fumadó / Maria Teresa Viadero / Carlos Rodrigo / Maria Méndez-Hernández / Eduardo López-Granados / Roger Colobran / Jacques G. Rivière /
    Pere Soler-Palacín / Aurora Pujol / Manel Esteller

    EClinicalMedicine, Vol 50, Iss , Pp 101515- (2022)

    A multicenter, retrospective study

    2022  

    Abstract: Summary: Background: Most children and adolescents infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain asymptomatic or develop a mild coronavirus disease 2019 (COVID-19) that usually does not require medical intervention. ...

    Abstract Summary: Background: Most children and adolescents infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain asymptomatic or develop a mild coronavirus disease 2019 (COVID-19) that usually does not require medical intervention. However, a small proportion of pediatric patients develop a severe clinical condition, multisystem inflammatory syndrome in children (MIS-C). The involvement of epigenetics in the control of the immune response and viral activity prompted us to carry out an epigenomic study to uncover target loci regulated by DNA methylation that could be altered upon the appearance of MIS-C. Methods: Peripheral blood samples were recruited from 43 confirmed MIS-C patients. 69 non-COVID-19 pediatric samples and 15 COVID-19 pediatric samples without MIS-C were used as controls. The cases in the two groups were mixed and divided into discovery (MIS-C = 29 and non-MIS-C = 56) and validation (MIS-C = 14 and non-MIS-C = 28) cohorts, and balanced for age, gender and ethnic background. We interrogated 850,000 CpG sites of the human genome for DNA methylation variants. Findings: The DNA methylation content of 33 CpG loci was linked with the presence of MIS-C. Of these sites, 18 (54.5%) were located in described genes. The top candidate gene was the immune T-cell mediator ZEB2; and others highly ranked candidates included the regulator of natural killer cell functional competence SH2D1B; VWA8, which contains a domain of the Von Willebrand factor A involved in the pediatric hemostasis disease; and human leukocyte antigen complex member HLA-DRB1; in addition to pro-inflammatory genes such as CUL2 and AIM2. The identified loci were used to construct a DNA methylation profile (EPIMISC) that was associated with MIS-C in both cohorts. The EPIMISC signature was also overrepresented in Kawasaki disease patients, a childhood pathology with a possible viral trigger, that shares many of the clinical features of MIS-C. Interpretation: We have characterized DNA methylation loci that are associated ...
    Keywords Multisystem inflammatory syndrome in children ; COVID-19 ; Kawasaki disease ; Epigenetics ; DNA methylation ; Medicine (General) ; R5-920
    Subject code 610
    Language English
    Publishing date 2022-08-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Impact of COVID19 pandemic on patients with rare diseases in Spain, with a special focus on inherited metabolic diseases

    M. Mar Rovira-Remisa / Mónica Moreira / Paula Sol Ventura / Pablo Gonzalez-Alvarez / Núria Mestres / Fredzzia Graterol Torres / Clara Joaquín / Agustí Rodríguez-Palmero Seuma / Maria del Mar Martínez-Colls / Ana Roche / Salvador Ibáñez-Micó / Eduardo López-Laso / María Jesús Méndez-Hernández / Marta Murillo / Laura Monlleó-Neila / Elena Maqueda-Castellote / Mireia del Toro Riera / Ana Felipe-Rucián / Maria Giralt-López /
    Elisenda Cortès-Saladelafont

    Molecular Genetics and Metabolism Reports, Vol 35, Iss , Pp 100962- (2023)

    2023  

    Abstract: Introduction: The Covid-19 pandemic soon became an international health emergency raising concern about its impact not only on physical health but also on quality of life and mental health. Rare diseases are chronically debilitating conditions with ... ...

    Abstract Introduction: The Covid-19 pandemic soon became an international health emergency raising concern about its impact not only on physical health but also on quality of life and mental health. Rare diseases are chronically debilitating conditions with challenging patient care needs. We aimed to assess the quality of life and mental health of patients with rare diseases in Spain, with a special focus on inherited metabolic disorders (IMD). Methods: A prospective case-control study was designed, comparing 459 patients suffering from a rare disease (including 53 patients with IMD) and 446 healthy controls. Quality of life (QoL) and mental health were assessed using validated scales according to age: KINDL-R and the Pediatric Symptom Checklist (PSC) for children and the WhoQoL-Bref questionnaire, GAD and PHQ-9 in adults. Results: First, children and adults (but not adolescents) with IMD showed greater psychological effects than controls (p = 0.022, p = 0.026 respectively). Second, when comparing QoL, only adult patients with IMD showed worse score than controls (66/100 vs 74,6/100 respectively, p = 0.017). Finally, IMD had better quality of life than other rare neurological and genetic diseases (p = 0.008) or other rare diseases (p < 0.001 respectively) but similar alteration of the mental status. Conclusions: Our data show that the pandemic had a negative impact on mental health that is more evident in the group of patients with IMD. Young age would behave as a protective factor on the perception of QoL. Furthermore, patients with IMD show a better QoL than other rare diseases.
    Keywords Rare diseases ; Quality of life ; Anxiety ; Depression ; Inherited metabolic disease ; Medicine (General) ; R5-920 ; Biology (General) ; QH301-705.5
    Subject code 610 ; 360
    Language English
    Publishing date 2023-06-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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    Inter-library loan at ZB MED

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  4. Article: Impact of COVID19 pandemic on patients with rare diseases in Spain, with a special focus on inherited metabolic diseases.

    Rovira-Remisa, M Mar / Moreira, Mónica / Ventura, Paula Sol / Gonzalez-Alvarez, Pablo / Mestres, Núria / Graterol Torres, Fredzzia / Joaquín, Clara / Seuma, Agustí Rodríguez-Palmero / Del Mar Martínez-Colls, Maria / Roche, Ana / Ibáñez-Micó, Salvador / López-Laso, Eduardo / Méndez-Hernández, María Jesús / Murillo, Marta / Monlleó-Neila, Laura / Maqueda-Castellote, Elena / Del Toro Riera, Mireia / Felipe-Rucián, Ana / Giralt-López, Maria /
    Cortès-Saladelafont, Elisenda

    Molecular genetics and metabolism reports

    2023  Volume 35, Page(s) 100962

    Abstract: Introduction: The Covid-19 pandemic soon became an international health emergency raising concern about its impact not only on physical health but also on quality of life and mental health. Rare diseases are chronically debilitating conditions with ... ...

    Abstract Introduction: The Covid-19 pandemic soon became an international health emergency raising concern about its impact not only on physical health but also on quality of life and mental health. Rare diseases are chronically debilitating conditions with challenging patient care needs. We aimed to assess the quality of life and mental health of patients with rare diseases in Spain, with a special focus on inherited metabolic disorders (IMD).
    Methods: A prospective case-control study was designed, comparing 459 patients suffering from a rare disease (including 53 patients with IMD) and 446 healthy controls. Quality of life (QoL) and mental health were assessed using validated scales according to age: KINDL-R and the Pediatric Symptom Checklist (PSC) for children and the WhoQoL-Bref questionnaire, GAD and PHQ-9 in adults.
    Results: First, children and adults (but not adolescents) with IMD showed greater psychological effects than controls (
    Conclusions: Our data show that the pandemic had a negative impact on mental health that is more evident in the group of patients with IMD. Young age would behave as a protective factor on the perception of QoL. Furthermore, patients with IMD show a better QoL than other rare diseases.
    Language English
    Publishing date 2023-03-06
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2821908-9
    ISSN 2214-4269
    ISSN 2214-4269
    DOI 10.1016/j.ymgmr.2023.100962
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Epigenome-wide association study of COVID-19 severity with respiratory failure

    Manuel Castro de Moura / Veronica Davalos / Laura Planas-Serra / Damiana Alvarez-Errico / Carles Arribas / Montserrat Ruiz / Sergio Aguilera-Albesa / Jesús Troya / Juan Valencia-Ramos / Valentina Vélez-Santamaria / Agustí Rodríguez-Palmero / Judit Villar-Garcia / Juan P. Horcajada / Sergiu Albu / Carlos Casasnovas / Anna Rull / Laia Reverte / Beatriz Dietl / David Dalmau /
    Maria J. Arranz / Laia Llucià-Carol / Anna M. Planas / Jordi Pérez-Tur / Israel Fernandez-Cadenas / Paula Villares / Jair Tenorio / Roger Colobran / Andrea Martin-Nalda / Pere Soler-Palacin / Francesc Vidal / Aurora Pujol / Manel Esteller

    EBioMedicine, Vol 66, Iss , Pp 103339- (2021)

    2021  

    Abstract: Background: Patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the coronavirus disease 2019 (COVID-19), exhibit a wide spectrum of disease behaviour. Since DNA methylation has been implicated in the ... ...

    Abstract Background: Patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the coronavirus disease 2019 (COVID-19), exhibit a wide spectrum of disease behaviour. Since DNA methylation has been implicated in the regulation of viral infections and the immune system, we performed an epigenome-wide association study (EWAS) to identify candidate loci regulated by this epigenetic mark that could be involved in the onset of COVID-19 in patients without comorbidities. Methods: Peripheral blood samples were obtained from 407 confirmed COVID-19 patients ≤ 61 years of age and without comorbidities, 194 (47.7%) of whom had mild symptomatology that did not involve hospitalization and 213 (52.3%) had a severe clinical course that required respiratory support. The set of cases was divided into discovery (n = 207) and validation (n = 200) cohorts, balanced for age and sex of individuals. We analysed the DNA methylation status of 850,000 CpG sites in these patients. Findings: The DNA methylation status of 44 CpG sites was associated with the clinical severity of COVID-19. Of these loci, 23 (52.3%) were located in 20 annotated coding genes. These genes, such as the inflammasome component Absent in Melanoma 2 (AIM2) and the Major Histocompatibility Complex, class I C (HLA-C) candidates, were mainly involved in the response of interferon to viral infection. We used the EWAS-identified sites to establish a DNA methylation signature (EPICOVID) that is associated with the severity of the disease. Interpretation: We identified DNA methylation sites as epigenetic susceptibility loci for respiratory failure in COVID-19 patients. These candidate biomarkers, combined with other clinical, cellular and genetic factors, could be useful in the clinical stratification and management of patients infected with the SARS-CoV-2. Funding: The Unstoppable campaign of the Josep Carreras Leukaemia Foundation, the Cellex Foundation and the CERCA Programme/Generalitat de Catalunya.
    Keywords Coronavirus ; SARS-CoV-2 ; COVID-19 ; Epigenetics ; DNA methylation ; Medicine ; R ; Medicine (General) ; R5-920
    Subject code 610
    Language English
    Publishing date 2021-04-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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