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  1. Article ; Online: Host genetic basis of COVID-19: from methodologies to genes.

    Zguro, Kristina / Fallerini, Chiara / Fava, Francesca / Furini, Simone / Renieri, Alessandra

    European journal of human genetics : EJHG

    2022  Volume 30, Issue 8, Page(s) 899–907

    Abstract: The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is having a massive impact on public health, societies, and economies worldwide. Despite the ongoing vaccination program, treating COVID-19 remains a high ... ...

    Abstract The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is having a massive impact on public health, societies, and economies worldwide. Despite the ongoing vaccination program, treating COVID-19 remains a high priority; thus, a better understanding of the disease is urgently needed. Initially, susceptibility was associated with age, sex, and other prior existing comorbidities. However, as these conditions alone could not explain the highly variable clinical manifestations of SARS-CoV-2 infection, the attention was shifted toward the identification of the genetic basis of COVID-19. Thanks to international collaborations like The COVID-19 Host Genetics Initiative, it became possible the elucidation of numerous genetic markers that are not only likely to help in explaining the varied clinical outcomes of COVID-19 patients but can also guide the development of novel diagnostics and therapeutics. Within this framework, this review delineates GWAS and Burden test as traditional methodologies employed so far for the discovery of the human genetic basis of COVID-19, with particular attention to recently emerged predictive models such as the post-Mendelian model. A summary table with the main genome-wide significant genomic loci is provided. Besides, various common and rare variants identified in genes like TLR7, CFTR, ACE2, TMPRSS2, TLR3, and SELP are further described in detail to illustrate their association with disease severity.
    MeSH term(s) COVID-19/genetics ; Humans ; Pandemics ; SARS-CoV-2/genetics
    Language English
    Publishing date 2022-05-27
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 1141470-4
    ISSN 1476-5438 ; 1018-4813
    ISSN (online) 1476-5438
    ISSN 1018-4813
    DOI 10.1038/s41431-022-01121-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Ultra-rare RTEL1 gene variants associate with acute severity of COVID-19 and evolution to pulmonary fibrosis as a specific long COVID disorder.

    Bergantini, Laura / Baldassarri, Margherita / d'Alessandro, Miriana / Brunelli, Giulia / Fabbri, Gaia / Zguro, Kristina / Degl'Innocenti, Andrea / Fallerini, Chiara / Bargagli, Elena / Renieri, Alessandra

    Respiratory research

    2023  Volume 24, Issue 1, Page(s) 158

    Abstract: Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a novel coronavirus that caused an ongoing pandemic of a pathology termed Coronavirus Disease 19 (COVID-19). Several studies reported that both COVID-19 and RTEL1 variants are ... ...

    Abstract Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a novel coronavirus that caused an ongoing pandemic of a pathology termed Coronavirus Disease 19 (COVID-19). Several studies reported that both COVID-19 and RTEL1 variants are associated with shorter telomere length, but a direct association between the two is not generally acknowledged. Here we demonstrate that up to 8.6% of severe COVID-19 patients bear RTEL1 ultra-rare variants, and show how this subgroup can be recognized.
    Methods: A cohort of 2246 SARS-CoV-2-positive subjects, collected within the GEN-COVID Multicenter study, was used in this work. Whole exome sequencing analysis was performed using the NovaSeq6000 System, and machine learning methods were used for candidate gene selection of severity. A nested study, comparing severely affected patients bearing or not variants in the selected gene, was used for the characterisation of specific clinical features connected to variants in both acute and post-acute phases.
    Results: Our GEN-COVID cohort revealed a total of 151 patients carrying at least one RTEL1 ultra-rare variant, which was selected as a specific acute severity feature. From a clinical point of view, these patients showed higher liver function indices, as well as increased CRP and inflammatory markers, such as IL-6. Moreover, compared to control subjects, they present autoimmune disorders more frequently. Finally, their decreased diffusion lung capacity for carbon monoxide after six months of COVID-19 suggests that RTEL1 variants can contribute to the development of SARS-CoV-2-elicited lung fibrosis.
    Conclusion: RTEL1 ultra-rare variants can be considered as a predictive marker of COVID-19 severity, as well as a marker of pathological evolution in pulmonary fibrosis in the post-COVID phase. This notion can be used for a rapid screening in hospitalized infected people, for vaccine prioritization, and appropriate follow-up assessment for subjects at risk. Trial Registration NCT04549831 ( www.
    Clinicaltrial: org ).
    MeSH term(s) Humans ; COVID-19/diagnosis ; COVID-19/genetics ; DNA Helicases/genetics ; Lung ; Post-Acute COVID-19 Syndrome/genetics ; Pulmonary Fibrosis/diagnosis ; Pulmonary Fibrosis/genetics ; SARS-CoV-2
    Chemical Substances DNA Helicases (EC 3.6.4.-) ; RTEL1 protein, human (EC 3.6.1.-)
    Language English
    Publishing date 2023-06-16
    Publishing country England
    Document type Multicenter Study ; Journal Article
    ZDB-ID 2041675-1
    ISSN 1465-993X ; 1465-993X
    ISSN (online) 1465-993X
    ISSN 1465-993X
    DOI 10.1186/s12931-023-02458-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Gain- and Loss-of-Function

    Baldassarri, Margherita / Zguro, Kristina / Tomati, Valeria / Pastorino, Cristina / Fava, Francesca / Croci, Susanna / Bruttini, Mirella / Picchiotti, Nicola / Furini, Simone / Gen-Covid Multicenter Study / Pedemonte, Nicoletta / Gabbi, Chiara / Renieri, Alessandra / Fallerini, Chiara

    Cells

    2022  Volume 11, Issue 24

    Abstract: Carriers of single pathogenic variants of ... ...

    Abstract Carriers of single pathogenic variants of the
    Language English
    Publishing date 2022-12-16
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells11244096
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Expanding the clinical spectrum associated with the PACS1 p.Arg203Trp mutational hot-spot: Two additional Italian patients.

    Bruno, Lucia Pia / Doddato, Gabriella / Baldassarri, Margherita / Rizzo, Caterina Lo / Resciniti, Sara / Bruttini, Mirella / Mirjam, Lista / Zguro, Kristina / Furini, Simone / Mencarelli, Maria Antonietta / Renieri, Alessandra / Ariani, Francesca

    American journal of medical genetics. Part A

    2022  Volume 191, Issue 1, Page(s) 284–288

    MeSH term(s) Humans ; Mutation ; Vesicular Transport Proteins/genetics
    Chemical Substances Vesicular Transport Proteins ; PACS1 protein, human
    Language English
    Publishing date 2022-10-09
    Publishing country United States
    Document type Letter
    ZDB-ID 2108614-X
    ISSN 1552-4833 ; 0148-7299 ; 1552-4825
    ISSN (online) 1552-4833
    ISSN 0148-7299 ; 1552-4825
    DOI 10.1002/ajmg.a.62984
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: A genome-wide association study for survival from a multi-centre European study identified variants associated with COVID-19 risk of death.

    Minnai, Francesca / Biscarini, Filippo / Esposito, Martina / Dragani, Tommaso A / Bujanda, Luis / Rahmouni, Souad / Alarcón-Riquelme, Marta E / Bernardo, David / Carnero-Montoro, Elena / Buti, Maria / Zeberg, Hugo / Asselta, Rosanna / Romero-Gómez, Manuel / Fernandez-Cadenas, Israel / Fallerini, Chiara / Zguro, Kristina / Croci, Susanna / Baldassarri, Margherita / Bruttini, Mirella /
    Furini, Simone / Renieri, Alessandra / Colombo, Francesca

    Scientific reports

    2024  Volume 14, Issue 1, Page(s) 3000

    Abstract: The clinical manifestations of SARS-CoV-2 infection vary widely among patients, from asymptomatic to life-threatening. Host genetics is one of the factors that contributes to this variability as previously reported by the COVID-19 Host Genetics ... ...

    Abstract The clinical manifestations of SARS-CoV-2 infection vary widely among patients, from asymptomatic to life-threatening. Host genetics is one of the factors that contributes to this variability as previously reported by the COVID-19 Host Genetics Initiative (HGI), which identified sixteen loci associated with COVID-19 severity. Herein, we investigated the genetic determinants of COVID-19 mortality, by performing a case-only genome-wide survival analysis, 60 days after infection, of 3904 COVID-19 patients from the GEN-COVID and other European series (EGAS00001005304 study of the COVID-19 HGI). Using imputed genotype data, we carried out a survival analysis using the Cox model adjusted for age, age2, sex, series, time of infection, and the first ten principal components. We observed a genome-wide significant (P-value < 5.0 × 10
    MeSH term(s) Humans ; COVID-19 ; Genome-Wide Association Study/methods ; Genetic Predisposition to Disease ; SARS-CoV-2 ; Genotype
    Language English
    Publishing date 2024-02-06
    Publishing country England
    Document type Multicenter Study ; Journal Article
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-024-53310-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Correction: SELP Asp603Asn and severe thrombosis in COVID-19 males.

    Fallerini, Chiara / Daga, Sergio / Benetti, Elisa / Picchiotti, Nicola / Zguro, Kristina / Catapano, Francesca / Baroni, Virginia / Lanini, Simone / Bucalossi, Alessandro / Marotta, Giuseppe / Colombo, Francesca / Baldassarri, Margherita / Fava, Francesca / Beligni, Giada / Di Sarno, Laura / Alaverdian, Diana / Palmieri, Maria / Croci, Susanna / Isidori, Andrea M /
    Furini, Simone / Frullanti, Elisa / Renieri, Alessandra / Mari, Francesca

    Journal of hematology & oncology

    2023  Volume 16, Issue 1, Page(s) 11

    Language English
    Publishing date 2023-02-15
    Publishing country England
    Document type Published Erratum
    ZDB-ID 2429631-4
    ISSN 1756-8722 ; 1756-8722
    ISSN (online) 1756-8722
    ISSN 1756-8722
    DOI 10.1186/s13045-023-01415-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: HLA-DPB1*13:01 associates with enhanced, and KIR2DS4*001 with diminished protection from developing severe COVID-19.

    Farias, Ticiana D J / Brugiapaglia, Silvia / Croci, Susanna / Magistroni, Paola / Curcio, Claudia / Zguro, Kristina / Fallerini, Chiara / Fava, Francesca / Pettini, Francesco / Kichula, Katherine M / Pollock, Nicholas R / Font-Porterias, Neus / Palmer, William H / Marin, Wesley M / Baldassarri, Margherita / Bruttini, Mirella / Hollenbach, Jill A / Hendricks, Audrey E / Meloni, Ilaria /
    Novelli, Francesco / Renieri, Alessandra / Furini, Simone / Norman, Paul J / Amoroso, Antonio

    HLA

    2023  Volume 103, Issue 1, Page(s) e15251

    Abstract: Extreme polymorphism of HLA and killer-cell immunoglobulin-like receptors (KIR) differentiates immune responses across individuals. Additional to T cell receptor interactions, subsets of HLA class I act as ligands for inhibitory and activating KIR, ... ...

    Abstract Extreme polymorphism of HLA and killer-cell immunoglobulin-like receptors (KIR) differentiates immune responses across individuals. Additional to T cell receptor interactions, subsets of HLA class I act as ligands for inhibitory and activating KIR, allowing natural killer (NK) cells to detect and kill infected cells. We investigated the impact of HLA and KIR polymorphism on the severity of COVID-19. High resolution HLA class I and II and KIR genotypes were determined from 403 non-hospitalized and 1575 hospitalized SARS-CoV-2 infected patients from Italy collected in 2020. We observed that possession of the activating KIR2DS4*001 allotype is associated with severe disease, requiring hospitalization (OR = 1.48, 95% CI 1.20-1.85, p
    MeSH term(s) Humans ; COVID-19/genetics ; SARS-CoV-2/genetics ; Alleles ; Receptors, KIR/genetics ; Genotype ; Autoantibodies/genetics ; HLA-DP beta-Chains
    Chemical Substances HLA-DPB1 antigen ; Receptors, KIR ; Autoantibodies ; KIR2DS4 protein, human ; HLA-DP beta-Chains
    Language English
    Publishing date 2023-10-18
    Publishing country England
    Document type Journal Article
    ZDB-ID 2845111-9
    ISSN 2059-2310 ; 2059-2302
    ISSN (online) 2059-2310
    ISSN 2059-2302
    DOI 10.1111/tan.15251
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: SPTBN5

    Khan, Amjad / Bruno, Lucia Pia / Alomar, Fadhel / Umair, Muhammad / Pinto, Anna Maria / Khan, Abid Ali / Khan, Alamzeb / Saima / Fabbiani, Alessandra / Zguro, Kristina / Furini, Simone / Mencarelli, Maria Antonietta / Renieri, Alessandra / Resciniti, Sara / Peña-Guerra, Karla A / Guzmán-Vega, Francisco J / Arold, Stefan T / Ariani, Francesca / Khan, Shahid Niaz

    Frontiers in molecular neuroscience

    2022  Volume 15, Page(s) 877258

    Abstract: Whole exome sequencing has provided significant opportunities to discover novel candidate genes for intellectual disability and autism spectrum disorders. Variants in the spectrin ... ...

    Abstract Whole exome sequencing has provided significant opportunities to discover novel candidate genes for intellectual disability and autism spectrum disorders. Variants in the spectrin genes
    Language English
    Publishing date 2022-06-17
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2452967-9
    ISSN 1662-5099
    ISSN 1662-5099
    DOI 10.3389/fnmol.2022.877258
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Carriers of ADAMTS13 Rare Variants Are at High Risk of Life-Threatening COVID-19

    Zguro, Kristina / Baldassarri, Margherita / Fava, Francesca / Beligni, Giada / Daga, Sergio / Leoncini, Roberto / Galasso, Lucrezia / Cirianni, Michele / Rusconi, Stefano / Siano, Matteo / Francisci, Daniela / Schiaroli, Elisabetta / Luchi, Sauro / Morelli, Giovanna / Martinelli, Enrico / Girardis, Massimo / Busani, Stefano / Parisi, Saverio Giuseppe / Panese, Sandro /
    Piscopo, Carmelo / Capasso, Mario / Tacconi, Danilo / Spertilli Raffaelli, Chiara / Giliberti, Annarita / Gori, Giulia / Katsikis, Peter D. / Lorubbio, Maria / Calzoni, Paola / Ognibene, Agostino / Bocchia, Monica / Tozzi, Monica / Bucalossi, Alessandro / Marotta, Giuseppe / Furini, Simone / GEN-COVID Multicenter Study / Renieri, Alessandra / Fallerini, Chiara

    Viruses. 2022 May 29, v. 14, no. 6

    2022  

    Abstract: Thrombosis of small and large vessels is reported as a key player in COVID-19 severity. However, host genetic determinants of this susceptibility are still unclear. Congenital Thrombotic Thrombocytopenic Purpura is a severe autosomal recessive disorder ... ...

    Abstract Thrombosis of small and large vessels is reported as a key player in COVID-19 severity. However, host genetic determinants of this susceptibility are still unclear. Congenital Thrombotic Thrombocytopenic Purpura is a severe autosomal recessive disorder characterized by uncleaved ultra-large vWF and thrombotic microangiopathy, frequently triggered by infections. Carriers are reported to be asymptomatic. Exome analysis of about 3000 SARS-CoV-2 infected subjects of different severities, belonging to the GEN-COVID cohort, revealed the specific role of vWF cleaving enzyme ADAMTS13 (A disintegrin-like and metalloprotease with thrombospondin type 1 motif, 13). We report here that ultra-rare variants in a heterozygous state lead to a rare form of COVID-19 characterized by hyper-inflammation signs, which segregates in families as an autosomal dominant disorder conditioned by SARS-CoV-2 infection, sex, and age. This has clinical relevance due to the availability of drugs such as Caplacizumab, which inhibits vWF–platelet interaction, and Crizanlizumab, which, by inhibiting P-selectin binding to its ligands, prevents leukocyte recruitment and platelet aggregation at the site of vascular damage.
    Keywords COVID-19 infection ; Severe acute respiratory syndrome coronavirus 2 ; heterozygosity ; leukocytes ; ligands ; metalloproteinases ; microangiopathy ; platelet aggregation ; risk ; thrombocytopenic purpura ; thrombosis
    Language English
    Dates of publication 2022-0529
    Publishing place Multidisciplinary Digital Publishing Institute
    Document type Article
    ZDB-ID 2516098-9
    ISSN 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v14061185
    Database NAL-Catalogue (AGRICOLA)

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  10. Article: Exome Sequencing in 200 Intellectual Disability/Autistic Patients: New Candidates and Atypical Presentations.

    Valentino, Floriana / Bruno, Lucia Pia / Doddato, Gabriella / Giliberti, Annarita / Tita, Rossella / Resciniti, Sara / Fallerini, Chiara / Bruttini, Mirella / Lo Rizzo, Caterina / Mencarelli, Maria Antonietta / Mari, Francesca / Pinto, Anna Maria / Fava, Francesca / Baldassarri, Margherita / Fabbiani, Alessandra / Lamacchia, Vittoria / Benetti, Elisa / Zguro, Kristina / Furini, Simone /
    Renieri, Alessandra / Ariani, Francesca

    Brain sciences

    2021  Volume 11, Issue 7

    Abstract: Intellectual disability (ID) and autism spectrum disorder (ASD) belong to neurodevelopmental disorders and occur in ~1% of the general population. Due to disease heterogeneity, identifying the etiology of ID and ASD remains challenging. Exome sequencing ( ...

    Abstract Intellectual disability (ID) and autism spectrum disorder (ASD) belong to neurodevelopmental disorders and occur in ~1% of the general population. Due to disease heterogeneity, identifying the etiology of ID and ASD remains challenging. Exome sequencing (ES) offers the opportunity to rapidly identify variants associated with these two entities that often co-exist. Here, we performed ES in a cohort of 200 patients: 84 with isolated ID and 116 with ID and ASD. We identified 41 pathogenic variants with a detection rate of 22% (43/200): 39% in ID patients (33/84) and 9% in ID/ASD patients (10/116). Most of the causative genes are genes responsible for well-established genetic syndromes that have not been recognized for atypical phenotypic presentations. Two genes emerged as new candidates:
    Language English
    Publishing date 2021-07-16
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2651993-8
    ISSN 2076-3425
    ISSN 2076-3425
    DOI 10.3390/brainsci11070936
    Database MEDical Literature Analysis and Retrieval System OnLINE

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